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8:00AM 11/13/2014 – 10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

REAL TIME Coverage of this Conference by Dr. Aviva Lev-Ari, PhD, RN – Director and Founder of LEADERS in PHARMACEUTICAL BUSINESS INTELLIGENCE, Boston http://pharmaceuticalintelligence.com

8:00 A.M. Welcome from Gary Gottlieb, M.D.

Opening Remarks:

Partners HealthCare is the largest healthcare organization in Massachusetts and whose founding members are Brigham and Women’s Hospital and Massachusetts General Hospital. Dr. Gottlieb has long been a supporter of personalized medicine and he will provide his vision on the role of genetics and genomics in healthcare across the many hospitals that are part of Partners HealthCare.

Opening Remarks and Introduction

Scott Weiss, M.D., M.S. @PartnersNews
Scientific Director, Partners HealthCare Personalized Medicine;
Associate Director, Channing Laboratory/
Professor of Medicine, Harvard Medical School 
@harvardmed

Welcome

Engine of innovations

  • lower cost – Accountable care
  • robust IT infrastructure on the Unified Medical Records
  • Lab Molecular Medicine and Biobanks
  • 1. Lab Molecular medicine
  • 2. Biobank
  • 3. Translations Genomics: RNA Sequencing
  • 4. Medical Records integration of coded diagnosis linked to Genomics

BIOBANKS – Samples and contact patients, return actionable procedures

LIFE STYLE SURVEY – supplements the medical record

GENOTYPING and SEQUENCING – less $50 per sequence available to researcher / investigators

RECRUITMENT – subject to biobank, own Consents – e-mail patient – consent online consenting — collects 16,000 patients per month – very successful Online Consent

LAB Molecular Medicine – CLIA — genomics test and clinical care – EGFR identified as a bio-marker to cancer in 3 month a test was available. Best curated medical exon databases Emory Genetics Lab (EMVClass) and CHOP (BioCreative and MitoMAP and MitoMASTER). Labs are renowned in pharmacogenomics and interpretability.

IT – GeneInsight – IT goal Clinicians empowered by a workflow geneticist assign cases, data entered into knowledge base, case history, GENEINSIGHT Lab — geneticists enter info in a codified way will trigger a report for the Geneticist – adding specific knowledge standardized report enters Medical Record. Available in many Clinics of Partners members.

Example: Management of Patient genetic profiles – Relationships built between the lab and the Clinician

Variety of Tools are in development

GenInsight Team –>> Pathology –>> Sunquest Relationship

The Future

Genetic testing –>> other info (Pathology, Exams, Life Style Survey, Meds, Imaging) — Integrated Medical Record

Clinic of the Future-– >> Diagnostics – Genomics data and Variants integrated at the Clinician desk

Gary Gottlieb, M.D. @PartnersNews
President and CEO, Partners HealthCare

Translational Science
Partners 6,000 MDs, MGH – 200 years as Teaching Hospital of HMS, BWH – magnets in HealthCare

2001  – Center for Genomics was started at Partners, 2008 Genomics and Other Omis, Population Health, PM – Innovations at Partners.

Please Click on Link  Video on 20 years of PartnersHealthcare

Video of Dr. Gottlieb at ECRI conference 2012

Why is personalized medicine  important to Partners?

From Healthcare system to the Specific Human Conditions

  • Lab translate results to therapy
  • Biobank +50,000 specimens links to Medical Records of patients – relevant to Clinician, Genomics to Clinical Applications

Questions from the Podium

  • test results are not yet available online for patients
  • clinicians and liability – delays from Lab to decide a variant needs to be reclassified – alert is triggered. Lab needs time to accumulated knowledge before reporting a change in state.
  • Training Clinicians in above type of IT infrastructure: Labs around the Nations deal with VARIANT RECLASSIFICATION- physician education is a must, Clinicians have access to REFERENCE links.
  • All clinicians accessing this IT infrastructure — are trained. Most are not yet trained
  • Coordination within Countries and Across Nations — Platforms are Group specific – PARTNERS vs the US IT Infrastructure — Genomics access to EMR — from 20% to 70% Nationwide during the Years of the Obama Adm.
  • Shakeout in SW linking Genetic Labs to reach Gold Standard

Click to see Advanced Medical Education Partners Offers

 

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx#sthash.qGbGZXXf.dpuf

@HarvardPMConf

#PMConf

@SachsAssociates

@PartnersNews

@MassGeneral

@HarvardHealth

@harvardmed

@BrighamWomens

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Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD


Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

Curator: Aviva Lev-Ari, PhD, RN

This article is Part VI in a Series of articles on Calcium Release Mechanism, the series consists of the following articles:

Part I: Identification of Biomarkers that are Related to the Actin Cytoskeleton

Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2012/12/10/identification-of-biomarkers-that-are-related-to-the-actin-cytoskeleton/

Part II: Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility

Larry H. Bernstein, MD, FCAP, Stephen Williams, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/26/role-of-calcium-the-actin-skeleton-and-lipid-structures-in-signaling-and-cell-motility/

Part III: Renal Distal Tubular Ca2+ Exchange Mechanism in Health and Disease

Larry H. Bernstein, MD, FCAP, Stephen J. Williams, PhD
 and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/02/renal-distal-tubular-ca2-exchange-mechanism-in-health-and-disease/

Part IV: The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets

Larry H Bernstein, MD, FCAP, Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/08/the-centrality-of-ca2-signaling-and-cytoskeleton-involving-calmodulin-kinases-and-ryanodine-receptors-in-cardiac-failure-arterial-smooth-muscle-post-ischemic-arrhythmia-similarities-and-differen/

Part V: Ca2+-Stimulated Exocytosis:  The Role of Calmodulin and Protein Kinase C in Ca2+ Regulation of Hormone and Neurotransmitter

Larry H Bernstein, MD, FCAP
and
Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/23/calmodulin-and-protein-kinase-c-drive-the-ca2-regulation-of-hormone-and-neurotransmitter-release-that-triggers-ca2-stimulated-exocytosis/

Part VI: Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/01/calcium-molecule-in-cardiac-gene-therapy-inhalable-gene-therapy-for-pulmonary-arterial-hypertension-and-percutaneous-intra-coronary-artery-infusion-for-heart-failure-contributions-by-roger-j-hajjar/

Part VII: Cardiac Contractility & Myocardium Performance: Ventricular Arrhythmias and Non-ischemic Heart Failure – Therapeutic Implications for Cardiomyocyte Ryanopathy (Calcium Release-related Contractile Dysfunction) and Catecholamine Responses

Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/28/cardiac-contractility-myocardium-performance-ventricular-arrhythmias-and-non-ischemic-heart-failure-therapeutic-implications-for-cardiomyocyte-ryanopathy-calcium-release-related-contractile/

Part VIII: Disruption of Calcium Homeostasis: Cardiomyocytes and Vascular Smooth Muscle Cells: The Cardiac and Cardiovascular Calcium Signaling Mechanism

Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/12/disruption-of-calcium-homeostasis-cardiomyocytes-and-vascular-smooth-muscle-cells-the-cardiac-and-cardiovascular-calcium-signaling-mechanism/

Part IXCalcium-Channel Blockers, Calcium Release-related Contractile Dysfunction (Ryanopathy) and Calcium as Neurotransmitter Sensor

Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Part X: Synaptotagmin functions as a Calcium Sensor: How Calcium Ions Regulate the fusion of vesicles with cell membranes during Neurotransmission

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/10/synaptotagmin-functions-as-a-calcium-sensor-how-calcium-ions-regulate-the-fusion-of-vesicles-with-cell-membranes-during-neurotransmission/

Part XI: Sensors and Signaling in Oxidative Stress

Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2013/11/01/sensors-and-signaling-in-oxidative-stress/

Part XII: Atherosclerosis Independence: Genetic Polymorphisms of Ion Channels Role in the Pathogenesis of Coronary Microvascular Dysfunction and Myocardial Ischemia (Coronary Artery Disease (CAD))

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/21/genetic-polymorphisms-of-ion-channels-have-a-role-in-the-pathogenesis-of-coronary-microvascular-dysfunction-and-ischemic-heart-disease/

This article has THREE parts:

Part I: Scientific Leader in Cardiology, Contributions by Roger J. Hajjar, MD to Gene Therapy

Part II: Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension

Part III: Cardiac Gene Therapy: Percutaneous Intra-coronary Artery Infusion for Heart Failure

The following two discoveries in Cardiac Gene Therapies represent the FRONTIER IN CARDIOLOGY for 2012 – 2013: Solution Advancement for Improving Myocardial Contractility

Part I: Scientific Leader in Cardiology, Contributions by Roger J. Hajjar, MD to Gene Therapy

Roger J. Hajjar, MD, a pioneering Mount Sinai researcher who has published cutting-edge studies on heart failure, has been named the recipient of the 2013 BCVS Distinguished Achievement Award by theAmerican Heart Association and the Council on Basic Cardiovascular Sciences. Dr. Hajjar, who is The Arthur and Janet C. Ross Professor of Medicine and Director of The Helmsley Trust Translational Research Center, will be honored at the American Heart Association’s Scientific Sessions Annual Conference later this year.

“Dr. Hajjar will receive the award for his groundbreaking contributions to developing gene therapy treatments for cardiac disease,” says Joshua Hare, MD, who is President-elect of the Council on Basic Cardiovascular Sciences. He will also be recognized for his work on behalf of the Council.

Over the years, Dr. Hajjar’s laboratory has made important basic science discoveries that were translated into clinical trials. Most recently, Dr. Hajjar and his researchers identified a possible new drug target for treating or preventing heart failure. Says Mark A. Sussman, PhD, a former president of the Council, “Dr. Hajjar was among the first, and certainly the most successful, in combining gene therapy and treatment of heart failure. He shows a relentless pursuit of translating basic science into real-world treatment of heart disease.”

This article was first published in Inside Mount Sinai.

http://blog.mountsinai.org/blog/roger-j-hajjar-md-to-be-honored-for-research/

John Hopkins, Distinguished Alumnus Award 2011

Roger J. Hajjar, Engr ’86
Dr. Roger Hajjar received his bachelor’s degree in biomedical engineering from Johns Hopkins University in 1986. A cardiologist and translational scientist, he is a leader in gene therapy techniques and model testing for cardiovascular diseases. Dr. Hajjar is professor of medicine and cardiology, and professor of gene and cell medicine at Mount Sinai Medical Center in New York, as well as research director of Mount Sinai’s Wiener Family Cardiovascular Research Laboratories. Dr. Hajjar was recruited to Mt. Sinai from Harvard Medical School where he was assistant professor of medicine and staff cardiologist in the Heart Failure & Cardiac Transplantation Center. He received his medical degree from Harvard Medical School and trained in internal medicine and cardiology at Massachusetts General Hospital in Boston. Dr. Hajjar has concentrated his research efforts on understanding the basic mechanisms of heart failure. He has developed gene transfer methods and techniques in the heart to improve contractility. Dr. Hajjar’s laboratory focuses on targeting signaling pathways in cardiac myocytes to improve contractile function in heart failure and to block signaling pathways in hypertrophy and apoptosis. Dr. Hajjar has significant expertise in gene therapy. In 1996, he won the Young Investigator Award of the American Heart Association (Council on Circulation). In 1999, Dr. Hajjar was awarded the prestigious Doris Duke Clinical Scientist award and won first prize at the Astra Zeneca Young Investigator Forum. Dr. Hajjar holds a number of NIH grants.

http://alumni.jhu.edu/distinguishedalumni2011

Dr Hajjar is the Director of the Cardiovascular Research Center, and the Arthur & Janet C. Ross Professor of Medicine at Mount Sinai School of Medicine, New York, NY. He received his BS in Biomedical Engineering from Johns Hopkins University and his MD from Harvard Medical School and the Harvard-MIT Division of Health Sciences & Technology. He completed his training in internal medicine, cardiology and research fellowships at Massachusetts General Hospital in Boston.

Dr. Hajjar is an internationally renowned scientific leader in the field of cardiac gene therapy for heart failure. His laboratory focuses on molecular mechanisms of heart failure and has validated the cardiac sarcoplasmic reticulum calcium ATPase pump, SERCA2a, as a target in heart failure, developed methodologies for cardiac directed gene transfer that are currently used by investigators throughout the world, and examined the functional consequences of SERCA2a gene transfer in failing hearts. His basic science laboratory remains one of the preeminent laboratories for the investigation of calcium cycling in failing hearts and targeted gene transfer in various animal models. The significance of Dr Hajjar’s research has been recognized with the initiation and recent successful completion of phase 1 and phase 2 First-in-Man clinical trials of SERCA2a gene transfer in patients with advanced heart failure under his guidance.

Prior to joining Mount Sinai, Dr. Hajjar served as Director of the Cardiovascular Laboratory of Integrative Physiology and Imaging at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. Dr. Hajjar has also been a staff cardiologist in the Heart Failure & Cardiac Transplantation Center at Massachusetts General Hospital.

Dr. Hajjar has won numerous awards and distinctions, including the Young Investigator Award of the American Heart Association. He was awarded a Doris Duke Clinical Scientist award and has won first prize at the Astra Zeneca Young Investigator Forum. He is a member of the American Society for Clinical Investigation. He was recently awarded the Distinguished Alumnus Award from Johns Hopkins University and the Mount Sinai Dean’s award for Excellence in Translational Science. He has authored over 260 peer-reviewed publications.

http://heart.sdsu.edu/~website/IRRI/Pages/faculty/roger-hajjar-md.html

Meet the Director of Mount Sinai’s Cardiovascular Research Center

“Cardiovascular diseases are the number one cause of death globally. In order to tackle them in all aspects, we must unite improved diagnostic techniques with more refined therapies.”

Roger J. Hajjar, MD, Director of the Cardiovascular Research Center, the Arthur & Janet C. Ross Professor of Medicine, Professor of Gene & Cell Medicine, Director of the Cardiology Fellowship Program, and Co-Director of the Transatlantic Cardiovascular Research Center, which combines Mount Sinai Cardiology Laboratories with those of the Universite de Paris – Madame Curie.

In the late 1990s, the possibility that discoveries in genetics and genomics could have a positive impact on the diagnosis, treatment, and prevention of cardiovascular diseases seemed to be just a distant promise. Today, a little more than a decade later, the promise is beginning to take shape. Roger J. Hajjar, MD and his multidisciplinary team of investigators are beginning to translate scientific findings into real therapies for cardiovascular diseases. As Director of the Cardiovascular Research Institute and a cardiologist by training, Dr. Hajjar guides the growth of a cutting-edge translational research laboratory, which is positioning Mount Sinai as the leader in cardiovascular genomics.

An internationally recognized scientific leader in the field of cardiac gene therapy for heart failure, Dr. Hajjar is expanding studies of the basic mechanisms of cardiac diseases and identification of high-risk groups and genomic predictors so that they can be part of the daily clinical care of patients. Unique biorepositories combined with cardiovascular areas of excellence across Mount Sinai make possible crucial genetic studies.

First Gene Therapy for Heart Failure

Under Dr. Hajjar’s leadership, the Cardiovascular Research Center has already developed the world’s first potential gene therapy for heart failure. Known as AAV1.SERCA2a, this therapy actually revives heart tissue that has stopped working properly. It has led to new treatment possibilities for patients with advanced heart failure, whose options used to be severely limited. The significance of this research has been recognized with the initiation and successful completion Phase 1 and Phase 2 First-in-Man clinical trials of SERCA2a gene transfer in patients with advanced heart failure. Phase 3 validation begins in 2011.

The Cardiovascular Research Center’s next research projects, already underway, focus on using novel gene therapy vectors to target diastolic heart failure, ventricular arrhythmias, pulmonary hypertension, and myocardial infarctions.

In addition to targeting signaling pathways to aid failing heart cells, ongoing work at the Cardiovascular Research Center involves studying how to block signaling pathways in cardiac hypertrophy as well as apoptosis. The laboratory team is also targeting a number of signaling pathways in the aging heart to improve dystolic function.

Prior to joining Mount Sinai in 2007, Dr. Hajjar served as Director of the Cardiovascular Laboratory of Integrative Physiology and Imaging at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. Dr. Hajjar has also been a staff cardiologist in the Heart Failure & Cardiac Transplantation Center at Massachusetts General Hospital. After earning a bachelors of science degree in Biomedical Engineering from Johns Hopkins University and a medical degree from Harvard Medical School and the Harvard-MIT Division of Health Sciences and Technology, he completed his training in internal medicine, cardiology and research fellowships at Massachusetts General Hospital in Boston.

Scientific Advisors

Roger J. Hajjar, MD, Co-Founder and a Scientific Advisor of Celladon Co, plans to commercialize AAV1.SERCA2a for the treatment of heart failure.
Dr. Roger J. Hajjar is the Director of the Cardiovascular Research Center at the Mt. Sinai School of Medicine. Previously, he was the Director of the Cardiovascular Laboratory of Integrative Physiology and Imaging at Massachusetts General Hospital (MGH) and Associate Professor of Medicine at Harvard Medical School. Dr. Hajjar has an active basic science laboratory and concentrates his research efforts on understanding the basic mechanisms of heart failure. He has developed gene transfer methods and techniques targeting the heart as a therapeutic modality to improve contractility in heart failure. Dr. Hajjar’s laboratory focuses on targeting signaling pathways in cardiac myocytes to improve contractile function in heart failure and to block signaling pathways in hypertrophy and apoptosis.

Gene Therapy: Volume 19, Issue 6 (June 2012)

Special Issue: Cardiovascular Gene Therapy

Guest Editor

Roger J Hajjar MD, Mount Sinai School of Medicine, New York, NY Director, Cardiovascular Research Institute, Arthur & Janet C Ross Professor of Medicine

SDF-1 in myocardial repair  

M S Penn, J Pastore, T Miller and R Aras

Gene Ther 19: 583-587; doi:10.1038/gt.2012.32

Abstract | Full Text | PDF

Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?  

R A Li

Gene Ther 19: 588-595; doi:10.1038/gt.2012.33

Abstract | Full Text | PDF

Sarcoplasmic reticulum and calcium cycling targeting by gene therapy  

J-S Hulot, G Senyei and R J Hajjar

Gene Ther 19: 596-599; advance online publication, May 17, 2012; doi:10.1038/gt.2012.34

Abstract | Full Text | PDF

Gene therapy for ventricular tachyarrhythmias  

J K Donahue

Gene Ther 19: 600-605; advance online publication, April 26, 2012; doi:10.1038/gt.2012.35

Abstract | Full Text | PDF

Prospects for gene transfer for clinical heart failure  

T Tang, M H Gao and H Kirk Hammond

Gene Ther 19: 606-612; advance online publication, April 26, 2012; doi:10.1038/gt.2012.36

Abstract | Full Text | PDF

Targeting S100A1 in heart failure  

J Ritterhoff and P Most

Gene Ther 19: 613-621; advance online publication, February 16, 2012; doi:10.1038/gt.2012.8

Abstract | Full Text | PDF

VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond  

M Giacca and S Zacchigna

Gene Ther 19: 622-629; advance online publication, March 1, 2012; doi:10.1038/gt.2012.17

Abstract | Full Text | PDF

Vein graft failure: current clinical practice and potential for gene therapeutics  

S Wan, S J George, C Berry and A H Baker

Gene Ther 19: 630-636; advance online publication, March 29, 2012; doi:10.1038/gt.2012.29

Abstract | Full Text | PDF

Percutaneous methods of vector delivery in preclinical models  

D Ladage, K Ishikawa, L Tilemann, J Müller-Ehmsen and Y Kawase

Gene Ther 19: 637-641; advance online publication, March 15, 2012; doi:10.1038/gt.2012.14

Abstract | Full Text | PDF

Lentiviral vectors and cardiovascular diseases: a genetic tool for manipulating cardiomyocyte differentiation and function  

E Di Pasquale, M V G Latronico, G S Jotti and G Condorelli

Gene Ther 19: 642-648; advance online publication, March 1, 2012; doi:10.1038/gt.2012.19

Abstract | Full Text | PDF

Intracellular transport of recombinant adeno-associated virus vectors  

M Nonnenmacher and T Weber

Gene Ther 19: 649-658; advance online publication, February 23, 2012; doi:10.1038/gt.2012.6

Abstract | Full Text | PDF

Gene delivery technologies for cardiac applications  

M G Katz, A S Fargnoli, L A Pritchette and C R Bridges

Gene Ther 19: 659-669; advance online publication, March 15, 2012; doi:10.1038/gt.2012.11

Abstract | Full Text | PDF

Cardiac gene therapy in large animals: bridge from bench to bedside  

K Ishikawa, L Tilemann, D Ladage, J Aguero, L Leonardson, K Fish and Y Kawase

Gene Ther 19: 670-677; advance online publication, February 2, 2012; doi:10.1038/gt.2012.3

Abstract | Full Text | PDF

Progress in gene therapy of dystrophic heart disease  

Y Lai and D Duan

Gene Ther 19: 678-685; advance online publication, February 9, 2012; doi:10.1038/gt.2012.10

Abstract | Full Text | PDF

Targeting GRK2 by gene therapy for heart failure: benefits above β-blockade  

J Reinkober, H Tscheschner, S T Pleger, P Most, H A Katus, W J Koch and P W J Raake

Gene Ther 19: 686-693; advance online publication, February 16, 2012; doi:10.1038/gt.2012.9

Abstract | Full Text | PDF

Directed evolution of novel adeno-associated viruses for therapeutic gene delivery  

M A Bartel, J R Weinstein and D V Schaffer

Gene Ther 19: 694-700; advance online publication, March 8, 2012; doi:10.1038/gt.2012.20

Abstract | Full Text | PDF

http://www.nature.com/gt/journal/v19/n6/index.html

Part II: Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension

Public release date: 30-Jul-2013

Contact: Lauren Woods
lauren.woods@mountsinai.org
212-241-2836
The Mount Sinai Hospital / Mount Sinai School of Medicine

Inhalable gene therapy may help pulmonary arterial hypertension patients

Gene therapy when inhaled may restore function of a crucial enzyme in the lungs to reverse deadly PAH

The deadly condition known as pulmonary arterial hypertension (PAH), which afflicts up to 150,000 Americans each year, may be reversible by using an inhalable gene therapy, report an international team of researchers led by investigators at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai.

In their new study, reported in the July 30 issue of the journal Circulation, scientists demonstrated that gene therapy administered through a nebulizer-like inhalation device can completely reverse PAH in rat models of the disease. In the lab, researchers also showed in pulmonary artery PAH patient tissue samples reduced expression of the SERCA2a, an enzyme critical for proper pumping of calcium in calcium compartments within the cells. SERCA2a gene therapy could be sought as a promising therapeutic intervention in PAH.

“The gene therapy could be delivered very easily to patients through simple inhalation — just like the way nebulizers work to treat asthma,” says study co-senior investigator Roger J. Hajjar, MD, Director of the Cardiovascular Research Center and the Arthur & Janet C. Ross Professor of Medicine and Professor of Gene & Cell at Icahn School of Medicine at Mount Sinai. “We are excited about testing this therapy in PAH patients who are in critical need of intervention.”

This same SERCA2a dysfunction also occurs in heart failure. This new study utilizes the same gene therapy currently being tested in patients to reverse congestive heart failure in a large phase III clinical trial in the United States and Europe.

“What we have shown is that gene therapy restores function of this crucial enzyme in diseased lungs,” says Dr. Hajjar. “We are delighted with these new findings because it suggests that a gene therapy that is already showing great benefit in congestive heart failure patients may be able to help PAH patients who currently have no good treatment options — and are in critical need of a life sustaining therapy.”

When SERCA2a is down-regulated, calcium stays longer in the cells than it should, and it induces pathways that lead to overgrowth of new and enlarged cells. According to researchers, the delivery of the SERCA2a gene produces SERCA2a enzymes, which helps both heart and lung cells restore their proper use of calcium.

“We are now on a path toward PAH patient clinical trials in the near future,” says Dr. Hajjar, who developed the gene therapy approach. Studies in large animal models are now underway. SERCA2a gene therapy has already been approved by the National Institutes of Health for human study.

A Simple Inhalation Corrects Deadly Dysfunction

PAH most commonly results from heart failure in the left side of the heart or from a pulmonary embolism, when clots in the legs travel to the lungs and cause blockages. When the lung is damaged from these conditions, the tissue starts to quickly produce new and enlarged cells, which narrows pulmonary arteries. This increases the pressure inside them. The high pressure in these arteries resists the heart’s effort to pump through them and the blood flow between the heart and lungs is reduced. The right side of the heart then must overcome the resistance and work harder to push the blood through the pulmonary arteries into the lungs. Over time, the right ventricle becomes thickened and enlarged and heart failure develops.

The gene therapy that Dr. Hajjar developed uses a modified adeno-associated viral-vector that is derived from a parvovirus. It works by introducing a healthy SERCA2a gene into cells, but this gene does not incorporate into a patient’s chromosome, according to the study’s lead author, Lahouaria Hadri, PhD, an Instructor of Medicine in Cardiology at Icahn School of Medicine at Mount Sinai.

“The clinical trials in congestive heart failure have shown already that the gene therapy is very safe,” says Dr. Hadri. Between 40-50 percent of individuals have antecedent antibodies to the adeno-associated vectors, so potential patients need to be screened before gene therapy to make sure they are eligible to receive the vectors. In patients without antibodies, the restorative enzyme gene therapy does not cause an immune response, according to Dr. Hadri.

The clinical application of the gene therapy for patients with PAH will most likely differ from those with heart failure. The replacement gene needs to be injected through the coronary arteries of heart failure patients using catheters, while in PAH patients, the gene will need to be administered through inhalation.

This study was supported by National Institutes of Health grants (K01HL103176, K08111207, R01 HL078691, HL057263, HL071763, HL080498, HL083156, and R01 HL105301).

Other study co-authors include Razmig G. Kratlian, MD, Ludovic Benard, PhD, Kiyotake Ishikawa, MD, Jaume Aguero, MD, Dennis Ladage, MD, Irene C.Turnbull, MD, Erik Kohlbrenner, BA, Lifan Liang, MD, Jean-Sébastien Hulot, MD, PhD, and Yoshiaki Kawase, MD, from Icahn School of Medicine at Mount Sinai; Bradley A. Maron, MD and the study’s co-senior author Jane A. Leopold, MD, from Brigham and Women’s Hospital and Harvard Medical School in Boston, MA; Christophe Guignabert, PhD, from Hôpital Antoine-Béclère, Clamart, France; Peter Dorfmüller, MD, PhD, and Marc Humbert, MD, PhD, both of the Hôpital Antoine-Béclère and INSERM U999, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson, France; Borja Ibanez, MD, from Fundación Centro Nacional de Investigaciones Cardiovasculares, Carlos III (CNIC), Madrid, Spain; and Krisztina Zsebo, PhD, of Celladon Corporation, San Diego, CA.

  • Dr. Hajjar and co-author Dr. Zsebo, have ownership interest in Celladon Corporation, which is developing AAV1.SERCA2a for the treatment of heart failure. Also,
  • Dr. Hajjar and co-authors Dr. Kawase and Dr. Ladage hold intellectual property around SERCA2a gene transfer as a treatment modality for PAH. In addition,
  • co-author Dr. Maron receives funding from Gilead Sciences, Inc. to study experimental pulmonary hypertension.
  • Other study co-authors have no financial interests to declare.

Therapeutic Efficacy of AAV1.SERCA2a in Monocrotaline-Induced Pulmonary Arterial Hypertension

  1. Lahouaria Hadri, PhD;
  2. Razmig G. Kratlian, MD;
  3. Ludovic Benard, PhD;
  4. Bradley A. Maron, MD;
  5. Peter Dorfmüller, MD, PhD;
  6. Dennis Ladage, MD;
  7. Christophe Guignabert, PhD;
  8. Kiyotake Ishikawa, MD;
  9. Jaume Aguero, MD;
  10. Borja Ibanez, MD;
  11. Irene C. Turnbull, MD;
  12. Erik Kohlbrenner, BA;
  13. Lifan Liang, MD;
  14. Krisztina Zsebo, PhD;
  15. Marc Humbert, MD, PhD;
  16. Jean-Sébastien Hulot, MD, PhD;
  17. Yoshiaki Kawase, MD;
  18. Roger J. Hajjar, MD*;
  19. Jane A. Leopold, MD*

+Author Affiliations


  1. From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (L.H., R.G.K., L.B., D.L., K.I., J.A., I.C.T., E.K., L.L., J.-S.H., Y.K., R.J.H.); Cardiovascular Medicine Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (B.A.M., J.A.L.); Hôpital Antoine-Béclère, Clamart, France (P.D., C.G., M.H.); INSERM U999, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson, France (P.D., M.H.); Fundación Centro Nacional de Investigaciones Cardiovasculares, Carlos III (CNIC), Madrid, Spain (B.I.); and Celladon Corporation, San Diego, CA (K.Z.).
  1. Correspondence to Lahouaria Hadri, PhD, Cardiovascular Research Center, Box 1030, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029. E-mail lahouaria.hadri@mssm.edu

Abstract

Background—Pulmonary arterial hypertension (PAH) is characterized by dysregulated proliferation of pulmonary artery smooth muscle cells leading to (mal)adaptive vascular remodeling. In the systemic circulation, vascular injury is associated with downregulation of sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) and alterations in Ca2+homeostasis in vascular smooth muscle cells that stimulate proliferation. We, therefore, hypothesized that downregulation of SERCA2a is permissive for pulmonary vascular remodeling and the development of PAH.

Methods and Results—SERCA2a expression was decreased significantly in remodeled pulmonary arteries from patients with PAH and the rat monocrotaline model of PAH in comparison with controls. In human pulmonary artery smooth muscle cells in vitro, SERCA2a overexpression by gene transfer decreased proliferation and migration significantly by inhibiting NFAT/STAT3. Overexpresion of SERCA2a in human pulmonary artery endothelial cells in vitro increased endothelial nitric oxide synthase expression and activation. In monocrotaline rats with established PAH, gene transfer of SERCA2a via intratracheal delivery of aerosolized adeno-associated virus serotype 1 (AAV1) carrying the human SERCA2a gene (AAV1.SERCA2a) decreased pulmonary artery pressure, vascular remodeling, right ventricular hypertrophy, and fibrosis in comparison with monocrotaline-PAH rats treated with a control AAV1 carrying β-galactosidase or saline. In a prevention protocol, aerosolized AAV1.SERCA2a delivered at the time of monocrotaline administration limited adverse hemodynamic profiles and indices of pulmonary and cardiac remodeling in comparison with rats administered AAV1 carrying β-galactosidase or saline.

Conclusions—Downregulation of SERCA2a plays a critical role in modulating the vascular and right ventricular pathophenotype associated with PAH. Selective pulmonary SERCA2a gene transfer may offer benefit as a therapeutic intervention in PAH.

Key Words:

  • Received January 24, 2013.
  • Accepted June 13, 2013.

http://circ.ahajournals.org/content/128/5/512.abstract?sid=9b3b4fcc-e158-4e5d-bb8b-125586e2ec12

Circulation.2013; 128: 512-523 Published online before print June 26, 2013,doi: 10.1161/​CIRCULATIONAHA.113.001585

Part III: Cardiac Gene Therapy: Percutaneous Intra-coronary Artery Infusion for Heart Failure

Etiology of Heart Failure

  • Alcoholic
  • Hypertensive
  • Idiopathic
  • Inflammatory
  • Ischemic
  • Pregnancy-related
  • Toxic
  • Valvular Heart DIsease

Administration of Cardiac Gene Therapy for Heart Failure: via Percutaneous Intra-coronary Artery Infusion

  • Gene delivery to viable myocardium

dominance and coronary artery anatomy from angiography determines infusion scenario

  • Antegrade epicardial coronary artery infusion over 10 minutes

60 mL divided into 1,2,3 infusions depending on anatomy

Delivered via commercially available angiographic injection system & guide or diagnostic catheters

Dr. Roger J. Hajjar of the Mount Sinai School of Medicine will present at the ASGCT 15th Annual Meeting during a Scientific Symposium entitled: Cell and Gene Therapy in Cardiovascular Disease on Wednesday, May 16, 2012 at 8:00 am. Below is a brief preview of his presentation.

Roger J. Hajjar, MD

Mount Sinai School of Medicine

New York, NY

Novel Developments in Gene Therapy for Cardiovascular Diseases

Chronic heart failure is a leading cause of hospitalization affecting nearly 6 million people in the U.S. with 670,000 new cases diagnosed every year. Heart failure leads to about 280,000 deaths annually.

Congestive heart failure remains a progressive disease with a desperate need for innovative therapies to reverse the course of ventricular dysfunction. The most common symptoms of heart failure are shortness of breath, feeling tired and swelling in the ankles, feet, legs and sometimes the abdomen. Recent advances in understanding the molecular basis of myocardial dysfunction, together with the evolution of increasingly efficient gene transfer technology have placed heart failure within reach of gene-based therapies.

One of the key abnormalities in both human and experimental HF is a defect in sarcoplasmic reticulum (SR) function, which controls Ca2+ handling in cardiac myocytes on a beat to beat basis. Deficient SR Ca2+ uptake during relaxation has been identified in failing hearts from both humans and animal models and has been associated with a decrease in the activity of the SR Ca2+-ATPase (SERCA2a).

Over the last ten years we have undertaken a program of targeting important calcium cycling proteins in experimental models of heart by somatic gene transfer. This has led to the completion of a first-in-man phase 1 clinical trial of gene therapy for heart failure using adeno-associated vector (AAV) type 1 carrying SERCA2a. In this Phase I trial, there was evidence of clinically meaningful improvements in functional status and/or cardiac function which were observed in the majority of patients at various time points. The safety profile of AAV gene therapy along with the positive biological signals obtained from this phase 1 trial has led to the initiation and recent completion of a phase 2 trial of AAV1.SERCA2a in NYHA class III/IV patients. In the phase 2 trial, gene transfer of SERCA2a was found to be safe and associated with benefit in clinical outcomes, symptoms, functional status, NT-proBNP and cardiac structure.

The 12 month data presented showed that heart failure, which is a progressive disease, became stabilized in high dose AAV1.SERCA2a-treated patients: heart failure symptoms, exercise tolerance, serum biomarkers and cardiac function essentially improved or remained the same while these parameters deteriorated substantially in patients treated with placebo and concurrent optimal drug and device therapy. More recently, the 2-year CUPID data from long-term follow-up demonstrate a durable benefit in preventing major cardiovascular events.

The recent successful and safe completion of the CUPID trial along with the start of more recent phase 1 trials usher a new era for gene therapy for the treatment of heart failure. Furthermore, novel AAV derivatives with high cardiotropism and resistant to neutralizing antibodies are being developed to target a large number of cardiovascular diseases.

http://www.execinc.com/hosted/emails/asgct/file/Hajjar2(1).pdf

Power Point Presentation on Cardiac Gene Therapy –

VIEW SLIDE SHOW

http://my.americanheart.org/idc/groups/heart-public/@wcm/@global/documents/downloadable/ucm_311680.pdf

Gene Therapy for Heart Failure

  1. Lisa Tilemann,
  2. Kiyotake Ishikawa,
  3. Thomas Weber,
  4. Roger J. Hajjar

+Author Affiliations


  1. From the Cardiovascular Research Center, Mount Sinai Medical Center, New York, NY.
  1. Correspondence to Roger J. Hajjar, MD, Mount Sinai Medical Center, One Gustave Levy Place, Box 1030, New York, NY 10029. E-mail roger.hajjar@mssm.edu

Abstract

Congestive heart failure accounts for half a million deaths per year in the United States. Despite its place among the leading causes of morbidity, pharmacological and mechanic remedies have only been able to slow the progression of the disease. Today’s science has yet to provide a cure, and there are few therapeutic modalities available for patients with advanced heart failure. There is a critical need to explore new therapeutic approaches in heart failure, and gene therapy has emerged as a viable alternative. Recent advances in understanding of the molecular basis of myocardial dysfunction, together with the evolution of increasingly efficient gene transfer technology, have placed heart failure within reach of gene-based therapy. The recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a), along with the start of more recent phase 1 trials, opens a new era for gene therapy for the treatment of heart failure.

Circulation Research.2012; 110: 777-793 doi: 10.1161/​CIRCRESAHA.111.252981

Key Words:

  • Received December 8, 2011.
  • Revision received January 29, 2012.
  • Accepted January 30, 2012.

Conclusions 

With a better understanding of the molecular mechanisms associated with heart failure and improved vectors with cardiotropic properties, gene therapy can now be considered as a viable adjunctive treatment to mechanical and pharmacological therapies for heart failure. In the coming years, more targets will emerge that are amenable to genetic manipulations, along with more advanced vector systems, which will undoubtedly lead to safer and more effective clinical trials in gene therapy for heart failure.

http://circres.ahajournals.org/content/110/5/777.full.pdf+html

Hijjar1
Figure 1.

AAV entry. 1 indicates receptor binding and endocytosis; 2, escape into cytoplasm; 3, nuclear import; 4, capsid disassembly; 5, double-strand synthesis; and 6, transcription.

Hijjar2

Figure 2.

Generation of mutant AAV library and directed evolution to identify cardiotropic AAVs. A, Creation of a library of AAVs through DNA shuffling.B, Selection of cardiotropic AAVs through directed evolution.

Hijjar3

Figure 3.

Antegrade coronary artery infusion. A, Coronary artery infusion. The vector is injected through a catheter without interruption of the coronary flow. B, Coronary artery infusion with occlusion of a coronary artery: The vector is injected through the lumen of an inflated angioplasty catheter. C, Coronary artery infusion with simultaneous blocking of a coronary artery and a coronary vein: The vector is injected through an inflated angioplasty catheter and resides in the coronary circulation until both balloons are deflated.

Hijjar4

Figure 4.

V-Focus system and retrograde coronary venous infusion. A, Recirculating antegrade coronary artery infusion: The vector is injected into a coronary artery, collected from the coronary sinus and after oxygenation readministered into the coronary artery. B, Retrograde coronary venous infusion with simultaneous blocking of a coronary artery and a coronary vein: The vector is injected into a coronary vein and resides in the coronary circulation until both balloons are deflated.

Hijjar5

Figure 5.

Direct myocardial injection and pericardial injection. A, Percutaneous myocardial injection: The vector is injected with an injection catheter via an endocardial approach.B, Surgical myocardial injection: The vector is injected via an epicardial approach. C, Percutaneous pericardial injection: The vector is injected via a substernal approach.

Hijjar6

Figure 6.

Excitation-contraction coupling in cardiac myocytes provides multiple targets for gene therapy.

SOURCE

http://circres.ahajournals.org/content/110/5/777.figures-only

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  • Up-regulation of sarcoplasmic reticulum Ca2+ uptake leads to cardiac hypertrophy, contractile dysfunction and early mortality in mice deficient in CASQ2Cardiovasc Res. 2013;98:297-306,
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http://circres.ahajournals.org/content/110/5/777.figures-only

For 154 References on Cardiac Gene Therapy

http://circres.ahajournals.org/content/110/5/777.full.pdf+html

Read Full Post »


Improved Results for Treatment of Persistent type 2 Endoleak after Endovascular Aneurysm Repair: Onyx Glue Embolization

Writer, Curator: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN 

 

 

This report is an evaluation of onyx glue use in endovascular aneurysm repair. Onyx® is a non-adhesive liquid embolic agent used for the pre-surgical embolization of brain Arteriovenous malformations (bAVM).
Onyx is comprised of EVOH (ethylene vinyl alcohol) copolymer dissolved in DMSO (dimethyl sulfoxide), and suspended micronized tantalum powder to provide contrast for visualization under fluoroscopy.
A DMSO compatible delivery micro catheter that is indicated for use in the neuro vasculature (e.g. Marathon™, Rebar® or UltraFlow™ HPC catheters) is used to access the embolization site.
Onyx is available in two product formulations, Onyx 18 (6% EVOH) and Onyx 34 (8% EVOH).
ONYX glue

Improved results using Onyx glue for the treatment of persistent type 2 endoleak after endovascular aneurysm repair. 

Abularrage CJ, Patel VI, Conrad MF, Schneider EB, Cambria RP, Kwolek CJ
Division of Vascular and Endovascular Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass 02114, USA.
J Vasc Surg. 2012 Sep;56(3):630-6.  http://dx.doi.org/10.1016/j.jvs.2012.02.038.  Epub 2012 May 8.
Persistent type 2 (PT2) endoleaks (present ≥ 6 months) after endovascular aneurysm repair are associated with adverse outcomes, and
  • selective secondary intervention is indicated in those patients with an expanding aneurysm sac.

This study evaluated the outcomes of secondary intervention for PT2.

From 1999 to 2007, 136 patients who underwent endovascular aneurysm repair developed PT2 and comprised the study cohort. Primary end points included
  • PT2 resolution (secondary interventional success) and
  • survival
 both  were evaluated using multiple logistic regression and Kaplan-Meier analyses
Fifty-one patients underwent a total of 68 secondary interventions for PT2 with expanding aneurysm sacs
  • with a median postsecondary interventional follow-up of 13.7 months.

Secondary interventions included

  • 20 inferior mesenteric artery coil embolizations,
  • 17 Onyx glue embolizations,
  • 11 aneurysm sac coil embolizations,
  • 10 non-Onyx glue embolizations,
  • 7 lumbar artery coil embolizations,
  • 2 open lumbar ligations, and 1 graft explant.
The overall secondary interventional success rate was 43% (29 of 68). Onyx glue embolization was associated with
  • a greater success rate when used as the initial secondary intervention (odds ratio, 59.61; 95% confidence interval, 4.78-742.73; P < .001). 
There was no difference in success between the different techniques when multiple secondary interventions were required. Five-year survival was 72% ± 0.08% and
  • was unrelated to any of the secondary interventional techniques.
Secondary intervention for PT2 is associated with success in less than half of all cases. Onyx glue embolization was associated with greater long-term success
  • when used as the initial secondary intervention.
Competition in the Ecosystem of Medical Devices in Cardiac and Vascular Repair: Heart Valves, Stents, Catheterization Tools and Kits for Open Heart and Minimally Invasive Surgery (MIS)  (Aviva Lev-Ari)
Vascular Repair: Stents and Biologically Active Implants (larryhbern)
Drug Eluting Stents: On MIT’s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES  (larryhbern)
Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents  (Aviva Lev-Ari)
Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Coronary Artery Disease (LMCAD) (larryhbern)
Transcatheter Aortic Valve Replacement (TAVR): Postdilatation to Reduce Paravalvular Regurgitation During TAVR with a Balloon-expandable Valve  (larryhbern)
Svelte Medical Systems’ Drug-Eluting Stent: 0% Clinically-Driven Events Through 12-Months in First-In-Man Study  (Aviva Lev-Ari)
Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone  (Justin Pearlman, Aviva Lev-Ari)
Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization (larryhbern)
Revascularization: PCI, Prior History of PCI vs CABG  (A Lev-Ari)
The ACUITY-PCI score: Will it Replace Four Established Risk Scores — TIMI, GRACE, SYNTAX, and Clinical SYNTAX  (A Lev-Ari)
Absorb™ Bioresorbable Vascular Scaffold: An International Launch by Abbott Laboratories (Aviva Lev-Ari)
Carotid Stenting: Vascular surgeons have pointed to more minor strokes in the stenting group and cardiologists to more myocardial infarctions in the CEA cohort. (A Lev-Ari)
Endovascular repair of cerebral aneurysm.

Endovascular repair of cerebral aneurysm. (Photo credit: Wikipedia)

Read Full Post »


Effect of Hospital Characteristics on Outcomes of Endovascular Repair of Descending Aortic Aneurysms in US Medicare Population

Writer and Curator: Larry H. Bernstein, MD, FCAP 

and

Curator: Aviva Lev-Ari, PhD, RN 

Impact of hospital volume and type on outcomes of open and endovascular repair of descending thoracic aneurysms in the United States Medicare population.

Patel VI, Mukhopadhyay S, Ergul E, Aranson N, …., Cambria RP.
Journal of vascular surgery 2013;    http://dx.doi.org/10.1016/j.jvs.2013.01.035

 

Open surgery for thoracic aortic aneurysm has had success, but it carries complication risks.  In 2004, a much less invasive procedure, thoracic endovascular repair (TEVAR) was introduced. It eliminated a need for open surgery in many patients, but not all were suitable candidtes .  The advances in endovascular technology and procedural breakthroughs  since it was introduced has contributed to a dramatic transformation of the specialty of thoracic aortic surgery. The decision of which patients require open surgery is necessarily determined by the limitations of the procedure and the condition of the patient.
Thoracic endovascular aortic repair (TEVAR) is a minimally invasive alternative to conventional open surgical reconstruction for the treatment of thoracic aortic aneurysm. TEVAR procedures can be challenging and, at times, extraordinarily difficult.  Meticulous assessment of anatomy and preoperative procedure planning are absolutely paramount to produce optimal outcomes. The rapidly Increased use of TEVAR has produced favorable outcomes of TEVAR compared with open abdominal repair for descending thoracic aortic aneurysms (DTAs).   But the success of these procedure depends on requisite skills, and following guidelines intended for use in quality-improvement programs that assess the standard of care expected from all physicians who perform TEVAR procedures.
Currently, there is a diverse array of endografts that are commercially available to treat the thoracic aorta. Multiple studies have demonstrated excellent outcomes of thoracic endovascular aortic repair for the treatment of thoracic aortic aneurysms, with less reported perioperative morbidity and mortality in comparison with conventional open repair. Additionally, similar outcomes have been demonstrated for the treatment of type B dissections. However, the technology remains relatively novel, and larger studies with longer term outcomes are necessary to more fully evaluate the role of endovascular therapy for the treatment of thoracic aortic disease.
The MGH/Partners vascular surgeons evaluated the effect of case volume and hospital teaching status on clinical outcomes of intact DTA repair to gain an insight into whether there was a variability in DTAs outcomes based on hospital size, patient mix, number of procedures, staff characteristics, and teaching status.  This study was needed for establishing the type of procedure most suited to the type of patient, and to obtain the most accurate analysis of cost requirements based on resource allocation for reimbursement purposes.
The Medicare Provider Analysis and Review (MEDPAR) data set (2004 to 2007) was queried to identify open repair or TEVAR for DTA. Hospitals were stratified by DTA volume into high volume (HV; ≥8 cases/y) or low volume (LV; <8 cases/y) and teaching or nonteaching. The effect of hospital variables on the primary study end point of 30-day mortality and secondary end points of 30-day complications and long-term survival after open repair and TEVAR DTA repair were studied using univariate testing, multivariable regression modeling, Kaplan-Meier survival analysis, and Cox proportional hazards regression modeling.
They identified 763 hospitals performing 3554 open repairs and 3517 TEVARs. Overall DTA repair increased (P < .01) from 1375 in 2004 to 1987 in 2007. The proportion of hospitals performing open repair significantly decreased from 95% in 2004 to 57% in 2007 (P < .01), whereas
  • those performing TEVAR increased (P < .01) from 24% to 76%.
Overall repair type shifted from open (74% in 2004, the year before initial commercial availability of TEVAR) to TEVAR (39% open in 2007; P < .01). The fraction of open repairs at LV hospitals
  • decreased from 56% in 2004 to 44% in 2007 (P < .01), whereas
  • TEVAR increased from 24% in 2004 to 51% in 2007 (P < .01).
Overall mortality during the study interval for
  •  open repair was 15% at LV hospitals vs 11% at HV hospitals (P < .01), whereas
  • TEVAR mortality was similar, at 3.9% in LV vs 5.5% in HV hospitals (P = .43).
LV was independently associated with increased mortality after open repair (odds ratio, 1.4; 95% confidence interval, 1.1-1.8; P < .01) but not after TEVAR. There was no independent effect of hospital teaching status on mortality or complications after open repair or TEVAR repair.
The total number of DTA repairs significantly increased after the introduction of TEVAR for DTA. Operative mortality for TEVAR is independent of hospital volume and type, whereas
  • mortality after open surgery is lower at HV hospitals.
While the TEVAR mortality is significantly less than that of open surgery, the mortality in open surgery is higher for LV hospitals.  The data suggests that TEVAR can be safely performed across a spectrum of hospitals, whereas open surgery should be performed only at HV hospitals.
  1. Standard of Practice for the Endovascular Treatment of Thoracic Aortic Aneurysms and Type B Dissections. Fanelli F, and  Dake MD.  Cardiovasc Intervent Radiol. 2009 September; 32(5): 849–860.  http://dx.doi.org/10.1007/s00270-009-9668-6  PMCID: PMC2744786
  2. Thoracic aortic aneurysms and dissections: endovascular treatment. Baril DT, Cho JS, Chaer RA, Makaroun MS. Division of Vascular Surgery, University of Pittsburgh Medical Center, Pittsburgh, PAMt Sinai J Med. 2010 May-Jun;77(3):256-69.  http://dx.doi.org/10.1002/msj.20178.

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Carotid Stenting: Vascular surgeons have pointed to more minor strokes in the stenting group and cardiologists to more myocardial infarctions in the CEA cohort. (A Lev-Ari)
https://pharmaceuticalintelligence.com/2012/09/21/carotid-stenting-vascular-surgeons-have-pointed-to-more-minor-strokes-in-the-stenting-group-and-cardiologists-to-more-myocardial-infarctions-in-the-cea-cohort/

New Drug-Eluting Stent Works Well in STEMI (A Lev-Ari)
https://pharmaceuticalintelligence.com/2012/08/22/new-drug-eluting-stent-works-well-in-stemi/

lobal Supplier Strategy for Market Penetration & Partnership Options (Niche Suppliers vs. National Leaders) in the Massachusetts Cardiology & Vascular Surgery Tools and Devices Market for Cardiac Operating Rooms and Angioplasty Suites (A Lev-Ari)
https://pharmaceuticalintelligence.com/2012/06/22/global-supplier-strategy-for-market-penetration-partnership-options-niche-suppliers-vs-national-leaders-in-the-massachusetts-cardiology-vascular-surgery-tools-and-devices-market-for-car/

Histopathological image of dissecting aneurysm...

Histopathological image of dissecting aneurysm of thoracic aorta in a patient without evidence of Marfan syndrome. The damaged aorta was surgically removed and replaced by artificial vessel. Victoria blue & HE stain. (Photo credit: Wikipedia)

Diagram of aortic aneurysm Figure A shows a no...

Diagram of aortic aneurysm Figure A shows a normal aorta. Figure B shows a thoracic aortic aneurysm (which is located behind the heart). Figure C shows an abdominal aortic aneurysm located below the arteries that supply blood to the kidneys. (Photo credit: Wikipedia)

Thoracic aorta

Thoracic aorta (Photo credit: Wikipedia)

Open Heart Surgery

Open Heart Surgery (Photo credit: Wikipedia)

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Abdominal Aortic Aneurysms (AAA): Albert Einstein’s Operation by Dr. Nissen

Reporter: Aviva Lev-Ari, PhD, RN

On June 11, 2013, I received the following comment by Dr. Miranda, to my article, an Interview with Dr. Richard Cambria, Chief Vascular Surgery, MGH, Boston

No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A Way To Know If I Have it?

Efrain Miranda, Ph.D. • It is true that abdominal aortic aneurysms (AAA) are mostly asymptomatic, until they rupture. By luck, some are identified. An example was a AAA found in Albert Einstein by Dr. Nissen when Einstein went for abdominal surgery for something completely unrelated! In my experience, I have found many AAA’s in individuals who had a totally different cause of death.
http://clinanat.com/mtd/153-aneurysm

I am presenting here the the CASE of an AAA found in Albert Einstein by Dr. Nissen when Einstein went for abdominal surgery for something completely unrelated!

A Moment in History

Dr. Rudolph Nissen
Dr. Rudolf Nissen
(1896 – 1981)

Dr Nissen’s life is extraordinary. Born in the city of Neisse, Germany in 1896, he was the son of a local surgeon. He studied medicine in the Universities of Munich, Marburg, and Breslau. He was the pupil of the famous pathologist Albert Aschoff (discoverer of the heart’s AV node, along with Sunao Tawara).

Nissen became a professor of surgery in Berlin, and in 1933 moved to Turkey where he was placed in charge of the Department of Surgery of the University of Istanbul. In 1939 he moved to the US, first to the Massachusetts General Hospital and later to the Jewish Hospital in Brooklyn, New York. After becoming a US citizen, he moved again in 1952 to Basel, Switzerland as Chief of the Department of Surgery, where he retired in 1967. He died in 1981.

His contributions to surgery are innumerable. He wrote over 30 books and 450 journal articles. Known for the development in 1956 of what is today known as the “Nissen fundoplication” for esophageal hiatus hernia surgery, Nissen also worked with his assistant, Dr. Mario Rossetti to develop the “floppy Nissen fundoplication”, also known as the “Nissen-Rossetti procedure”. This would be enough to honor this man, still, he (with Sauerbruch) performed the first lung lobectomy and the first pneumonectomy (called then a total pneumonectomy). In 1949 he performed the first esophagectomy with a gastroesophagostomy.

His personal life is even more interesting. Drafted at 20, he fought in WWI and was wounded several times. In 1933, under the Nazi regime,  he was ordered to fire all the Jewish-German assistants under his care. Being Jewish himself, he was told that he would keep his job, Nissen could not take this. He resigned his position and moved out of Germany.

Another little known fact is that he operated on Albert Einstein in 1948. He operated on Einstein because of intestinal cysts. Having found a developing abdominal aortic aneurysm, he reinforced it with cellophane, undoubtedly giving his patient a few extra years to live. Einstein died in 1955.

As a personal side note, our good friend Dr. Aaron Ruhalter scrubbed in with Dr. Nissen while serving as a surgical resident at the Brooklyn Jewish Hospital!

Sources:
1. “Rudolf Nissen: The man behind the fundoplication” Schein et al. Surgery 1999;125:347-53 
2. “Rudolf Nissen (1896–1981)-Perspective” Liebermann-Meffert, D. J Gastrointest Surg (2010) 14 (Suppl 1):S58–S61
3. “The Life of Rudolf Nissen: Advancing Surgery Through Science and Principle” Fults, DW; Taussky, P. World J Surg (2011) 35:1402–1408 
4. “Total Pneumonectomy” Nissen, R. Ann Thorac Surg 1980; 29:390-394 
5. “Historical Development of Pulmonary Surgery” Nissen, R. Am J Surg 80: Jan 1955 9- 15 áclav Treitz (1819-1872): Czechoslovakian Pathoanatomist and Patriot” Fox, RS; Fox, CG; Graham, WP. World J. Surg. 9, 361-366, 1985 
Original image courtesy of Universität Basel.

http://clinanat.com/mtd/153-aneurysm


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No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A Way To Know If I Have it?

Curator: Aviva Lev-Ari, PhD, RN

I shadowed Dr. Cambria in the Operating Room at MGH in January 2005 while he performed Carotid Endarterectomy following Aortic Valve Replacement performed by Dr. Jennifer D. Walker  in a sequence, first the Valve replacement, then the Endarterectomy.

Aneurysm

Published on Thursday, 15 November 2012 | Print | Email
This word has a Greek origin from the terms [aneurusma], composed of [ana] meaning “complete or throughout”, and [eurus] meaning “wide”, a “complete widening or dilation”. It is used to refer to the dilation of an artery. Aneurysms can be formed in any artery, although they have some preferred sites. The most common aneurysms are found in the aorta, arterial circle of Willis, the root of the cerebral arteries, and internal carotid arteries.Biomechanical studies suggest that once an aneurysm forms it will generally progress in its dilation until aneurysmal rupture. Because of turbulent flow within the aneurysm large clots are usually formed, which in turn can cause emboli.The image shows an excised infrarenal aortic abdominal aneurysm (AAA). The two common iliac arteries can be seen. If you click on the image you will be able to see the same aneurysm opened through its posterior wall and the clot that was contained inside.Photography by D.M.Klein  Abdominal Aortic Aneurysm

http://clinanat.com/mtd/153-aneurysm

On 6/11/2013, Efrain Miranda, Ph.D. commented on this article, as follows:

It is true that abdominal aortic aneurysms (AAA) are mostly asymptomatic, until they rupture. By luck, some are identified. An example was a AAA found in Albert Einstein by Dr. Nissen when Einstein went for abdominal surgery for something completely unrelated! In my experience, I have found many AAA’s in individuals who had a totally different cause of death.

Dr. Richard Cambria describes an Aortic Aneurysm and recalls the numerous risk factors associated with the condition.

VIEW VIDEO

http://www.empowher.com/aortic-aneurysm/content/there-are-no-early-symptoms-there-way-know-if-i-have-aortic-aneurysm-it-rupt

By Dr. Richard Cambria Expert April 12, 2011 – 10:08am

 

Dr. Cambria:
An aortic aneurysm can be most simply thoughts of as a weakening or ballooning of the aorta which is the body’s major and largest blood vessel. That’s important because this ballooning or weakening can eventually lead to the aneurysm bursting, which is usually a fatal event.

Aneurysms have been referred to as the ‘silent killer’ because in most cases these aortic aneurysms cause no symptoms or problems prior to bursting. Most aortic aneurysms occur in older patients, but there are a clearly defined set of risk factors which makes certain patients at higher risk of developing aortic aneurysms. These include, most importantly, a family history of aortic aneurysm disease, and by family history I mean, if your mother or father or a brother or sister had an aortic aneurysm, you are clearly at increased risk of developing an aneurysm.

20% of the patients that we treat for aortic aneurysms have a positive family history of aneurysm disease. You are also at higher risk for developing an aortic aneurysm if you are female, if you have a history of high blood pressure, if you have been a cigarette smoker, and if you have chronic obstructive pulmonary disease or emphysema, which is in turn related to long-term cigarette smoking.

If you are at risk for developing an aortic aneurysm there are simple diagnostic x-ray studies such as ultrasounds and CAT scans to accurately diagnose number one, whether or not an aneurysm is present, and more importantly, if it is present, to measure just how large it is because that’s the single most important factor in determining whether or not your aneurysm needs to be treated.

It’s important to detect and monitor aortic aneurysms before they reach the stage of bursting because treatment is then usually successful with an expected excellent recovery. Treatment of aortic aneurysms today is very effective and involves replacing the aneurysm with an artificial blood vessel.

There are a variety of different surgical treatments, some of them including minimally invasive operations known as stent grafts, which are applied today in many patients.

Mass General has been a leader in the northeast in the successful management of aortic aneurysms. More than a decade ago, we formed the Mass General Thoracic Aortic Center, which is a team-approach of vascular surgeons, cardiac or heart surgeons, and cardiologists to effectively manage thoracic aneurysms which are often the most challenging and clinically complex to treat.

About Dr. Richard Paul Cambria, M.D.:
Richard P. Cambria, M.D. is Professor of Surgery at Harvard Medical School and Chief, Division of Vascular/Endovascular Surgery at Massachusetts General Hospital. Dr. Cambria received his medical degree from the College of Physicians and Surgeons, Columbia University, in 1977. He trained in general and vascular surgery at Massachusetts General Hospital.

http://www.empowher.com/aortic-aneurysm/content/there-are-no-early-symptoms-there-way-know-if-i-have-aortic-aneurysm-it-rupt

Education & Awards

Dr. Cambria graduated from Columbia University, New York. He has 15 awards.

Awards
One of America’s Leading Experts on:
Abdominal Aortic Aneurysm
Aortic Aneurysm
Aortic Diseases
Aortic Rupture
Arterial Occlusive Diseases
Blood Vessel Prosthesis Implantation
Carotid Endarterectomy
Carotid Stenosis
Kidney Failure
Mesenteric Vascular Occlusion
Spinal Cord Ischemia
Thoracic Aortic Aneurysm
Vascular Surgical Procedures
Castle Connolly America’s Top Doctors® (2002 – 2012)
Top Ten Doctors (2012)
Vascular Surgery, Downtown, Boston, MA

http://www.vitals.com/doctors/Dr_Richard_Cambria.html#ixzz2VqxwIwMK

Publications & Research

Dr. Cambria has contributed to 164 publications.
Title Giant Cell Aortitis of the Ascending Aorta Without Signs or Symptoms of Systemic Vasculitis is Associated with Elevated Risk of Distal Aortic Events.
Date February 2012
Journal Arthritis and Rheumatism
Title Long-term Outcomes of Patients Undergoing Endovascular Infrainguinal Interventions with Single-vessel Peroneal Artery Runoff.
Date May 2011
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Management of Diseases of the Descending Thoracic Aorta in the Endovascular Era: a Medicare Population Study.
Date October 2010
Journal Annals of Surgery
Excerpt Read excerpt

Title The Effects of Systemic Hypothermia on a Murine Model of Thoracic Aortic Ischemia Reperfusion.
Date August 2010
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Long-term Outcomes of Diabetic Patients Undergoing Endovascular Infrainguinal Interventions.
Date August 2010
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Preoperative Variables Predict Persistent Type 2 Endoleak After Endovascular Aneurysm Repair.
Date August 2010
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Surgical Management of Descending Thoracic Aortic Disease: Open and Endovascular Approaches: a Scientific Statement from the American Heart Association.
Date August 2010
Journal Circulation
Title Balloon Expandable Stents Facilitate Right Renal Artery Reconstruction During Complex Open Aortic Aneurysm Repair.
Date March 2010
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Preoperative Functional Status Predicts Perioperative Outcomes After Infrainguinal Bypass Surgery.
Date March 2010
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Intermediate-term Outcomes of Endovascular Treatment for Symptomatic Chronic Mesenteric Ischemia.
Date February 2010
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title A Multicenter Clinical Trial of Endovascular Stent Graft Repair of Acute Catastrophes of the Descending Thoracic Aorta.
Date December 2009
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Effect of Pj34 on Spinal Cord Tissue Viability and Gene Expression in a Murine Model of Thoracic Aortic Reperfusion Injury.
Date December 2009
Journal Vascular and Endovascular Surgery
Excerpt Read excerpt

Title Secondary Intervention After Endovascular Abdominal Aortic Aneurysm Repair.
Date October 2009
Journal Annals of Surgery
Excerpt Read excerpt

Title Aortic Remodeling After Endovascular Repair of Acute Complicated Type B Aortic Dissection.
Date September 2009
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Significant Perioperative Morbidity Accompanies Contemporary Infrainguinal Bypass Surgery: an Nsqip Report.
Date September 2009
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Pj34, a Poly-adp-ribose Polymerase Inhibitor, Modulates Visceral Mitochondrial Activity and Cd14 Expression Following Thoracic Aortic Ischemia-reperfusion.
Date August 2009
Journal American Journal of Surgery
Excerpt Read excerpt

Title Thoracoabdominal Aneurysm Repair: Hybrid Versus Open Repair.
Date July 2009
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Successful Use of Bivalirudin for Combined Carotid Endarterectomy and Coronary Revascularization with the Use of Cardiopulmonary Bypass in a Patient with an Elevated Heparin-platelet Factor 4 Antibody Titer.
Date April 2009
Journal Anesthesia and Analgesia
Excerpt Read excerpt

Title Atherosclerotic Peripheral Vascular Disease Symposium Ii: Controversies in Carotid Artery Revascularization.
Date January 2009
Journal Circulation
Title Functional Outcome After Thoracoabdominal Aneurysm Repair.
Date December 2008
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Outcomes Following Endovascular Abdominal Aortic Aneurysm Repair (evar): an Anatomic and Device-specific Analysis.
Date August 2008
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Zenith Abdominal Aortic Aneurysm Endovascular Graft.
Date August 2008
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Spinal Cord Complications After Thoracic Aortic Surgery: Long-term Survival and Functional Status Varies with Deficit Severity.
Date August 2008
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Five-year Results of Endovascular Treatment with the Gore Tag Device Compared with Open Repair of Thoracic Aortic Aneurysms.
Date June 2008
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Aortic Aneurysms.
Date May 2008
Journal Journal of the American College of Radiology : Jacr
Title International Controlled Clinical Trial of Thoracic Endovascular Aneurysm Repair with the Zenith Tx2 Endovascular Graft: 1-year Results.
Date March 2008
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Contemporary Management of Descending Thoracic and Thoracoabdominal Aortic Aneurysms: Endovascular Versus Open.
Date February 2008
Journal Circulation
Title Contemporary Management of Carotid Stenosis: Carotid Endarterectomy is Here to Stay.
Date January 2008
Journal Perspectives in Vascular Surgery and Endovascular Therapy
Excerpt Read excerpt

Title Long-term Durability of Open Abdominal Aortic Aneurysm Repair.
Date November 2007
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Commentary On: Mas Jl, Chatellier G, Beyssen B, Et Al. Endarterectomy Versus Stenting in Patients with Symptomatic Severe Carotid Stenosis. N Engl J Med. 2006;355:1660-1671.
Date November 2007
Journal Perspectives in Vascular Surgery and Endovascular Therapy
Excerpt Read excerpt

Title Defining the High-risk Patient for Carotid Endarterectomy: an Analysis of the Prospective National Surgical Quality Improvement Program Database.
Date October 2007
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Persistent Type 2 Endoleak After Endovascular Repair of Abdominal Aortic Aneurysm is Associated with Adverse Late Outcomes.
Date July 2007
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Restenosis After Eversion Vs Patch Closure Carotid Endarterectomy.
Date July 2007
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Surgical Revascularization Versus Endovascular Therapy for Chronic Mesenteric Ischemia: a Comparative Experience.
Date July 2007
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Comparison of Risk-adjusted 30-day Postoperative Mortality and Morbidity in Department of Veterans Affairs Hospitals and Selected University Medical Centers: Vascular Surgical Operations in Men.
Date July 2007
Journal Journal of the American College of Surgeons
Excerpt Read excerpt

Title Thoracoabdominal Aneurysm Repair: a 20-year Perspective.
Date March 2007
Journal The Annals of Thoracic Surgery
Excerpt Read excerpt

Title Stent-graft Versus Open-surgical Repair of the Thoracic Aorta: Mid-term Results.
Date January 2007
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Intermediate Results of Percutaneous Endovascular Therapy of Femoropopliteal Occlusive Disease: a Contemporary Series.
Date October 2006
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Long-term Outcomes After Endovascular Abdominal Aortic Aneurysm Repair: the First Decade.
Date October 2006
Journal Annals of Surgery
Excerpt Read excerpt

Title Poly Adenosine Diphosphate-ribose Polymerase Inhibitor Pj34 Abolishes Systemic Proinflammatory Responses to Thoracic Aortic Ischemia and Reperfusion.
Date August 2006
Journal Journal of the American College of Surgeons
Excerpt Read excerpt

Title Contemporary Results of Open Surgical Repair of Descending Thoracic Aortic Aneurysms.
Date August 2006
Journal Seminars in Vascular Surgery
Excerpt Read excerpt

Title Commentary on “extra-anatomic Visceral Revascularization and Endovascular Stent-grafting for Complex Thoracoabdominal Aortic Lesions”.
Date May 2006
Journal Perspectives in Vascular Surgery and Endovascular Therapy
Title Multi-institutional Pivotal Trial of the Zenith Tx2 Thoracic Aortic Stent-graft for Treatment of Descending Thoracic Aortic Aneurysms: Clinical Study Design.
Date May 2006
Journal Perspectives in Vascular Surgery and Endovascular Therapy
Excerpt Read excerpt

Title Aortic Dissection: Perspectives in the Era of Stent-graft Repair.
Date March 2006
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Title Current Results of Open Surgical Repair of Descending Thoracic Aortic Aneurysms.
Date March 2006
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Title Late Results of Combined Carotid and Coronary Surgery Using Actual Versus Actuarial Methodology.
Date December 2005
Journal The Annals of Thoracic Surgery
Excerpt Read excerpt

Title Contemporary Results of Angioplasty-based Infrainguinal Percutaneous Interventions.
Date November 2005
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Pj34, a Poly-adp-ribose Polymerase Inhibitor, Modulates Renal Injury After Thoracic Aortic Ischemia/reperfusion.
Date October 2005
Journal Surgery
Excerpt Read excerpt

Title Safety and Efficacy of Reoperative Carotid Endarterectomy: a 14-year Experience.
Date July 2005
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Determinants of Carotid Endarterectomy Anatomic Durability: Effects of Serum Lipids and Lipid-lowering Drugs.
Date May 2005
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Early Outcomes of Endovascular Versus Open Abdominal Aortic Aneurysm Repair in the National Surgical Quality Improvement Program-private Sector (nsqip-ps).
Date May 2005
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Thoracoabdominal Aneurysm Repair: Anesthetic Management.
Date March 2005
Journal International Anesthesiology Clinics
Title Endovascular Treatment of Thoracic Aortic Aneurysms: Results of the Phase Ii Multicenter Trial of the Gore Tag Thoracic Endoprosthesis.
Date March 2005
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Poly(adenosine Diphosphate Ribose) Polymerase Inhibition Modulates Spinal Cord Dysfunction After Thoracoabdominal Aortic Ischemia-reperfusion.
Date March 2005
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Current Status of Thoracoabdominal Aneurysm Repair.
Date November 2004
Journal Advances in Surgery
Title Stenting for Carotid-artery Stenosis.
Date October 2004
Journal The New England Journal of Medicine
Title Carotid Endarterectomy at the Millennium: What Interventional Therapy Must Match.
Date September 2004
Journal Annals of Surgery
Excerpt Read excerpt

Title Surgical Management of Popliteal Artery Embolism at the Turn of the Millennium.
Date June 2004
Journal Annals of Vascular Surgery
Excerpt Read excerpt

Title Regional Hypothermia with Epidural Cooling for Prevention of Spinal Cord Ischemic Complications After Thoracoabdominal Aortic Surgery.
Date April 2004
Journal Seminars in Thoracic and Cardiovascular Surgery
Excerpt Read excerpt

Title Preservation of Renal Function with Surgical Revascularization in Patients with Atherosclerotic Renovascular Disease.
Date February 2004
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Durability of Aortouniiliac Endografting with Femorofemoral Crossover: 4-year Experience in the Evt/guidant Trials.
Date June 2003
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Late Aortic and Graft-related Events After Thoracoabdominal Aneurysm Repair.
Date February 2003
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Surgical Treatment of Complicated Distal Aortic Dissection.
Date October 2002
Journal Seminars in Vascular Surgery
Excerpt Read excerpt

Title Thoracoabdominal Aneurysm Repair: Results with 337 Operations Performed over a 15-year Interval.
Date October 2002
Journal Annals of Surgery
Excerpt Read excerpt

Title Clinical Outcome of Internal Iliac Artery Occlusions During Endovascular Treatment of Aortoiliac Aneurysmal Diseases.
Date October 2002
Journal Journal of Vascular and Interventional Radiology : Jvir
Excerpt Read excerpt

Title Evolving Experience with Thoracic Aortic Stent Graft Repair.
Date July 2002
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Clinical Failures of Endovascular Abdominal Aortic Aneurysm Repair: Incidence, Causes, and Management.
Date July 2002
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Regarding “analysis of Predictive Factors for Progression of Type B Aortic Intramural Hematoma with Computed Tomography”.
Date July 2002
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Title Contemporary Management of Aortic Branch Compromise Resulting from Acute Aortic Dissection.
Date July 2001
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Endovascular Stent-graft in Abdominal Aortic Aneurysms: the Relationship Between Patent Vessels That Arise from the Aneurysmal Sac and Early Endoleak.
Date June 2001
Journal Radiology
Excerpt Read excerpt

Title Regional Hypothermia with Epidural Cooling for Spinal Cord Protection During Thoracoabdominal Aneurysm Repair.
Date April 2001
Journal Seminars in Vascular Surgery
Excerpt Read excerpt

Title Endovascular Repair of Abdominal Aortic Aneurysms: Current Status and Future Directions.
Date August 2000
Journal Ajr. American Journal of Roentgenology
Title Epidural Cooling for Spinal Cord Protection During Thoracoabdominal Aneurysm Repair: A Five-year Experience.
Date July 2000
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Utility and Reliability of Endovascular Aortouniiliac with Femorofemoral Crossover Graft for Aortoiliac Aneurysmal Disease.
Date July 2000
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

Title Surgical Renal Artery Reconstruction Without Contrast Arteriography: the Role of Clinical Profiling and Magnetic Resonance Angiography.
Date January 2000
Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Excerpt Read excerpt

http://www.vitals.com/doctors/Dr_Richard_Cambria/credentials
http://www.vitals.com/doctors/Dr_Richard_Cambria/credentials#ixzz2VqyhFZVd

Cambria RP, Brewster DC, Lauterbach SR, Kaufman JA, Geller SC, Fan CM, Greenfield A, Hilgenberg A, Clouse WD. Evolving experience with thoracic aortic stent-graft repair. J Vasc Surg 2002:35:1129-36.

Cambria, RP, Clouse WD, Davison JK, Dunn PF, Corey M, Dorer D. Thoracoabdominal aneurysm repair: Results with 337 operations performed over a 15 year interval. Ann Surg 2002;236-471-79.

Cambria RP, Lauterbach SR, Brewster DC, Gertler JP, LaMuraglia GM, Isselbacher EM, Hilgenberg AD, Moncure AC. Contemporary management of aortic branch compromise secondary to acute aortic dissections. J Vasc Surg 2001;331185-92.

Cambria RP and Black JH. Aortic dissection perspectives for the vascular/endovascular surgeon. In Rutherford (ed) Comprehensive Vascular and Endovascular Surgery 6 th , W. B. Saunders, Inc. (in press, 2004).

Cambria RP, Marone LK, Cloud WD, Dorer, DJ, Brewster, DC, LaMuraglia, GM, Watkins, MT, Kwolek, CJ. Preservation of renal functions with surgical revascularization in patients with atherosclerotic renovascular disease. J Vasc Surg 2004; 10.023.

Abdominal Aortic Aneurysm – Case Study

by

Angela Rodriguez-Wong, MD, RVT, RPVI

Lois Eliassi, BS, RVT

http://www.navixdiagnostix.com/downloads/Navix%20-%20Q1%20’13%20Ultrasound%20Solutions.pdf

An aneurysm is defined as a focally dilated segment of an artery that is 1.5 times its normal diameter and involves all three arterial walls (intima, media and adventitia). Aneurysms can be found in the common femoral and popliteal arteries in the lower extremities, the splenic, mesenteric, and renal arteries in the abdomen, and also in the intracranial vessels. However, the most common is an abdominal aortic aneurysm (AAA) involving the aorta and iliac arteries.

Abdominal aortic aneurysms are generally asymptomatic and are discovered accidentally either by physician palpation or by a radiologic examination such as a chest or abdominal X-ray. The risk factors that increase the probability of developing a AAA are primarily smoking and family history. An abdominal aortic aneurysm can rupture and, according to the Centers for Disease Control and Prevention, ruptured AAA was the 10th leading cause of death in males between the ages of 65-74 in the United States in 2000.

The preferred method of screening for AAA is diagnostic ultrasound. According to the Journal of Vascular Surgery, diagnostic ultrasound performed by a registered vascular technologist has a sensitivity of 100 percent and a specificity of 96 percent for the detection of an infrarenal AAA. The abdominal aorta is considered aneurysmal when it measures >3.0 cm.

Because of its accuracy, diagnostic ultrasound not only has become an integral part in diagnosing AAA but is also an integral part in the evaluation of disease progression, the preoperative AAA evaluation, and the follow-up of AAA surgical repair. It is important to note that a rupture of an AAA is a surgical emergency and is difficult to evaluate with ultrasound due to the inability to easily demonstrate abdominal free fluid. If a rupture is suspected, it is recommended that other imaging modalities such as CT be employed to better demonstrate the ruptured aneurysm and any intra-abdominal free fluid.

Case Study – 

Abdominal Aortic Aneurysm – A 77 year-old male

Angela Rodriguez-Wong, MD, RVT, RPVI

Lois Eliassi, BS, RVT

Figure 1 Distal abdominal aortic aneurysm with mural thrombus.

pic1

Figure 2 Bifurcation of the aorta.

pic2

Case Study: A 77 year-old male with a past medical history of diabetes, hypertension, arthritis, aortic valve disease and heavy smoking was referred to Eastern Vascular Diagnostic Center with a 4.2 centimeter aneurysm. The patient denied any family history of aneurysm and is allergic to intravenous contrast. A physical exam found the patient alert with a blood pressure of 100/60 mmHg, a pulse of 58 and respiration of 16. Auscultation found a bruit in the left carotid artery, clear lungs, and a regular heart rhythm with an aortic systolic murmur. The patient had a well healed sub-costal incision on his abdomen. The physician was unable to palpate the aneurysms. The patient had an aortic valve replacement in 2007 and also a cholecystectomy. On May 12, 2012, a magnetic resonance imaging (MRI) scan without contrast was performed on the patient’s abdomen. The MRI found an AAA measuring greater than 3 cm with extensive plaque near the bifurcation. The aneurysm extended into the right common iliac artery (CIA) measuring 4.2 cm and into the left CIA measuring 3.1 cm. The MRI exam did not include the pelvis, so the extent of the iliac aneurysms was not clear. On July 31, 2012, the ultrasound was performed, demonstrating normal ankle brachial index (right-1.2, left-1.1) and a AAA measuring 3.9 cm which extended into the right and left CIA. The maximum diameter of the right CIA measures 4.1 cm with mural thrombus creating a residual lumen of 2.0 cm. The maximum diameter of the left CIA measures 4.3 cm, there is also mural thrombus noted but without significant appreciable diameter reduction within the vessel. A computed tomography (CT) scan of the abdomen and pelvis without contrast was performed on July 18th confirming the infrarenal AAA with extension into the iliac arteries bilaterally.

Surgery is recommended when an AAA reaches 5.0-5.5 cm in a male and 4.5-5.0 cm in females. Surgery, depending on the aneurysm, can be an open repair or an endovascular repair. In this patient, despite the size of the AAA being 4.1 cm, the disease also involved the bilateral common iliacs prompting the need for surgical intervention. The patient was cleared by cardiology and on July 31st had an AAA and bilateral Iliac aneurysm resection with a re-implantation of the inferior mesenteric artery and an Aorta to right Hypogastric bypass to maintain pelvic perfusion.

The U.S. Preventive Services Task Force has released a statement summarizing recommendations for screening for AAA. It states that screening benefits patients who have a relatively high risk for dying from an aneurysm; major risk factors are age 65 years or older, male sex, and smoking at least 100 cigarettes in a lifetime. The guideline recommends one-time screening with ultrasound for AAA in men 65 to 75 years of age who have ever smoked. No recommendation was made for or against screening in men 65 to 75 years of age who have never smoked, and it recommended against screening women. Men with a strong family history of AAA should be counseled about the risks and benefits of screening as they approach 65 years of age.

Angela Rodriguez-Wong, MD, RVT, RPVI 

awong@navixdiagnostix.com

Lois Eliassi, BS, RVT

leliassi@navixdiagnostix.com

Figure 3 Sagittal image of the right common iliac artery demonstrating the measurement of the aneurysm and the true lumen.

pic3

Figure 4 Coronal view of the left common iliac artery.

pic4

REFERENCES 

1. Anderson RN. Deaths: Leading causes for 2000. Natl Vital Stat Rep. 2002;50:1–85.

2. Kent KC, Zwolak RM, Jaff MR, et al. Screening for abdominal aortic aneurysm. J Vasc Surg. 2004;39:267–9.

3. Upchurch G Jr, Schaub T. Abdominal aortic aneurysm. American Family Physician. 2006;73(7), 1198-1204. http://www.aafp.org/afp/2006/0401/p1198.html

http://www.navixdiagnostix.com/downloads/Navix%20-%20Q1%20’13%20Ultrasound%20Solutions.pdf

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Reporter: Aviva Lev-Ari, PhD, RN

Immunomodulatory Therapeutic Antibodies for Cancer

 

 http://www.immunotherapiescongress.com/Conferences_Overview.aspx?id=124174

ImmunotherapiesCongress.com

August 13-15, 2013 • Hilton Boston Back Bay Hotel • Boston, MA Final Agenda

Register by May 17 and Save up to $300!

Organized by:

Cambridge Healthtech Institute

Inaugural Immunomodulator Antibodies for Cancer

August 14-15

Inaugural Emerging Cancer Immunotherapies and Vaccines

August 13-14

Sessions Include:

Cancer Biology and Biomarkers

• Emerging Cancer

Immunotherapies & Vaccines

• Clinical Development of

Immunomodulatory Antibodies

• Bispecific Immunomodulatory

Antibodies

Keynote Presentations:

The Promise of T-Cell Engineering

Michel Sadelain, M.D., Ph.D., Director, Center

for Cell Engineering & Gene Transfer and

Gene Expression Laboratory, Memorial Sloan-

Kettering Cancer Center

Immune Monitoring on

Pre-Surgical Clinical Trials with

a Novel Checkpoint Blockade

Agent, Anti-CTLA-4

Padmanee Sharma, M.D., Associate Professor,

Genitourinary Medical Oncology, University of

Texas MD Anderson Cancer Center

Co-Located Event

Eighth Annual

Novel Vaccines:

Innovations & Adjuvants

To Advance the Science of Vaccines

Immuno The

Congress

herapies Immune System Modulation

for Novel Cancer Treatments

ImmunotherapiesCongress.com

Short Courses:

Melanoma Biology and Immunotherapies

Monday, August 12

Manufacturing Vaccines:

New Approaches, New Technologies

Wednesday, August 14

ImmunotherapiesCongress.com 2

Pre-Conference Short Course *

Monday, August 12 • 2:00-5:00PM

Melanoma Biology and

Immunotherapies

Significant advances have been made in the understanding of the molecular

underpinnings of melanoma development and progression and in elucidating

the mechanisms by which these tumors escape immune surveillance. This

session will address the current understanding of somatic genetic alterations

that serve as the fundamental building blocks for malignant transformation

in melanoma and as the basis for the first generation of molecular targeted

therapies. Immune recognition of melanoma has been long recognized and

underlies melanoma’s relatively unique responsiveness to cytokine-based

immunotherapy. However, understanding of the negative immunomodulatory

regulators that prevent elimination of melanoma has led to novel therapeutic

approaches that manipulate effector antitumor T cell function.

Instructors:

Keith T. Flaherty, M.D., Associate Professor, Department of Medicine, Harvard Medical

School; Director, Termeer Center for Targeted Therapy, Cancer Center, Massachusetts

General Hospital

Jennifer Wargo, M.D., Surgical Oncologist, Massachusetts General Hospital; Instructor,

Harvard Medical School

Dinner Short Course*

Wednesday, August 14 • 6:30-9:30pm

Manufacturing Vaccines:

New Approaches, New Technologies

Novel vaccine production platforms are changing vaccines, affecting efficacy,

and steering manufacturing away from egg-based production. This course will

look at how vaccine production is being innovated, and how these innovations

are affecting the way vaccines work. New technologies, such as cell culturebased

production and using the BEVS (Baculovirus Expression Vector System),

are opening the door to improved vaccines. Join us for this intimate discussion

of how vaccine production is being revolutionized.

Instructors:

Sue Behrens, Ph.D., Consultant, Biologic, Vaccine & Sterile Products Manufacturing

Technology, SB Executive Consulting, LLC (former Senior Director of Biological Sciences

& Strategy, Vaccine & Sterile Operations at Merck)

Todd Talarico, Ph.D., Vice President, Manufacturing, Medicago-USA

*Separate registration required

Conference Hotel:

Hilton Boston Back Bay Hotel

40 Dalton Street

Boston, MA 02115

Phone: 617-236-1100

Discounted Room Rate: $195 s/d

Discounted Room Rate Cut-off Date: July 15, 2013

Please visit our conference website to make your

reservations online or call the hotel directly to

reserve your sleeping accommodations. Identify

yourself as a Cambridge Healthtech Institute

conference attendee to receive the reduced room

rate. Reservations made after the cut-off date

or after the group room block has been filled

(whichever comes first) will be accepted on a

space- and rate-availability basis. Rooms are

limited, so please book early.

HOTEL & TRAVEL INFORMATION

Flight Discounts:

To receive a 5% or greater discount on all American Airline flights please use one of the following

methods:

• Call 1-800-433-1790 use Conference code (8283BJ)

• Go online http://www.aa.com enter Conference code (8283BJ) in promotion

discount box

• Contact Rona Meizler, Great International Travel 1-617-559-3735

Car Rental Discounts:

Special discount rentals have been established with Hertz for this conference. Please use one of the

following methods:

• Call HERTZ, 800-654-3131 use our Hertz Convention Number (CV): 04KL0002

• Go online http://www.hertz.com use our Hertz Convention Number (CV): 04KL0002

3 ImmunotherapiesCongress.com

Inaugural

Emerging Cancer Immunotherapies and Vaccines

Next-Generation Targets and Strategies

August 13-14

Using lessons learned from early cancer vaccines and immunotherapeutics, a new wave of programs are underway that promise improved efficacy and

safety over a wider range of cancers. Emerging Cancer Immunotherapies and Vaccines will examine new targets and strategies in this space, along with

important studies in preclinical development associated with developing these programs into successful drug products. Speakers will offer approaches to

resolve the most challenging steps in the transition of these programs from research into clinical development.

TUESDAY , AUGUST 13, 2013

7:30 am Main Conference Registration and Morning Coffee

8:05 Chairperson’s Opening Remarks

T Cell Immunotherapy Strategies

»»8:15 Op ening Keynote Presentation

The Promise of T Cell Engineering

Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering & Gene Transfer and

Gene Expression Laboratory, Memorial Sloan-Kettering Cancer Center

T cell engineering offers a unique means to overcome the immune escape

stratagems used by tumors to elude immune rejection. The genetic

reprogramming of patient T cells can thus be used to enforce tumor

recognition, improve T cell survival, augment T cell expansion, generate

memory lymphocytes and offset T cell anergy and immune suppression.

Using “second-generation chimeric antigen receptors” (CARs), recent clinical

studies support the merit of this novel immunotherapy.

9:00 It Takes Two to Tango: Fine Tuning of Tumor Cells and T

Lymphocytes for Maximized Anti-Tumor Activity

Daniel J. Powell, Jr., M.D., Assistant Professor, Pathology and Laboratory Medicine, Perelman

School of Medicine, University of Pennsylvania

Genetic engineering with chimeric immune receptors now allows for rapid

de novo generation of autologous T cells with potent anti-tumor activity for

adoptive cell transfer therapy for cancer. Still, low target antigen expression

by tumor cells and antigen expression on normal tissues may render therapy

ineffective or potentially toxic. We have identified agents that sensitize tumor

cells to immune attack and made advances in T cell engineering strategies to

better direct T cells to tumor antigen and confine T cell activity to tumor.

9:30 Improved Cancer Immunotherapy through CD134 plus

CD137 Dual Co-Stimulation

Adam J. Adler, Ph.D., Associate Professor of Immunology, University of Connecticut

T cell-mediated anti-tumor immunity is dampened by tolerance mechanisms

that evolved to prevent autoimmunity. Since tolerance largely results as

a consequence of insufficient co-stimulation during antigenic priming, costimulatory

receptor agonists can program tumor-specific T cell expansion and

effector differentiation. In particular, dual administration of agonists to CD134 plus

CD137 activates multiple immune cells with tumoricidal potential including NK

cells, cytotoxic CD8+ T cells, and surprisingly, cytotoxic CD4+ T cells.

10:00 Refreshment Break

Cancer Biology and Biomarkers

10:30 Vascular Normalization as an Emerging Strategy to

Enhance Cancer Immunotherapy

Rakesh K. Jain, Ph.D., Andrew Werk Cook Professor of Tumor Biology, Harvard Medical

School; Director, E.L. Steele Laboratory of Tumor Biology, Department of Radiation Oncology,

Massachusetts General Hospital

The immunosuppressive tumor microenvironment remains a limiting factor

for anti-cancer vaccine therapies. In addition, tumors systemically alter

immune cells’ function via secretion of cytokines such as VEGF, a major proangiogenic

cytokine. Hence, anti-angiogenic treatment may be an effective

modality to potentiate immunotherapy. I will discuss the effects of VEGF

on anti-tumor immune responses, and propose a potentially translatable

strategy to re-engineer the tumor immune microenvironment and improve

cancer immunotherapy.

11:00 Advances in Biomarker Validation and Trial Design for

Antitumor Immunotherapy

Susan R. Slovin, M.D., Ph.D., Genitourinary Oncology Service, Sidney Kimmel Center for Prostate

and Urologic Cancers, Memorial Sloan–Kettering Cancer Center

Conventional imaging modalities have been the mainstay of assessing

treatment response. Recent data suggests that evaluating circulating tumor

cells may provide insight regarding changes in the tumor cells’ overall

behavior. Immunologic treatments often do not impact the cancer with

immediacy; a means of determining whether an immunologic target is hit

and whether it impacts the tumor’s biology remains a challenge. Changes in

T cell populations or myeloid suppressor cells may reflect potential impact on

the intra- and extra-tumoral milieu.

11:30 Exploring Synergy between Targeted Therapy and

Immunotherapy

Zachary Cooper, Ph.D., Postdoctoral Research Associate, Surgical Oncology, Massachusetts

General Hospital

Recent advances in the treatment of melanoma include the use of BRAFtargeted

therapy and immune checkpoint inhibitors, though each of

these treatments alone has its limitation. There is increasing evidence

for synergy between these modalities. Treatment with a BRAF inhibitor

results in enhanced melanoma antigen expression and a more favorable

microenvironment. Exploring the potential synergy using mouse models is

necessary in overcoming monotherapy limitations.

12:00pm Sponsored Presentations (Opportunities Available:

Contact Suzanne Carroll at 781-972-5452 or scarroll@healthtech.com

for more information)

12:30 Luncheon Presentation (Opportunity Available)

or Lunch on Your Own

Emerging Cancer Immunotherapies

1:55 Chairperson’s Opening Remarks

2:00 Synergism Between Anti-Tumor Antibodies and PKExtended

IL-2

K. Dane Wittrup, Ph.D., Dubbs Professor, Chemical Engineering and Biological Engineering, Koch

Institute for Integrative Cancer Research, Massachusetts Institute of Technology

We have found that combination treatment with anti-tumor antibody and an

IL-2 Fc fusion exerts a significantly stronger suppression of tumor growth

than either agent alone. This effect depends on the presence of both CD8+

T cells and neutrophils, indicating a close cooperation between innate and

cellular immunity. Strong potential exists for further synergy between antitumor

antibodies and the new generation of T cell-directed immunotherapies.

ImmunotherapiesCongress.com 4

2:30 Identifying New Cancer Immunotherapy Targets for T Cells

Robert Holt, Ph.D., Senior Scientist and Head of Sequencing, British Columbia Cancer Agency,

Canada

Effective cancer immunotherapy relies on effective tumor antigens. However,

most variations that distinguish tumor cells from normal cells are sporadic,

and their immunogenicity is undetermined. High throughput genomic

analysis is a useful approach for evaluating the potential immunogenicity

of individual tumors and identifying new candidate antigens for follow-on

validation. We are using two methods for T cell antigen discovery that will be

described, including tumor genome sequencing and computational epitope

prediction, plus deep TCR sequencing of tumor-associated T cells.

3:00 Immunomodulatory Antibody-Fusion Proteins for Cancer

Immunotherapy

Dafne Müller, Ph.D., Researcher, Institute of Cell Biology and Immunology, University of Stuttgart,

Germany

Cytokines of the common cytokine receptor γ-chain family and costimulatory

members of the B7- and TNF-family have shown great potential

to support the generation and development of an antitumor immune

response. In order to improve the efficacy of such molecules at the tumor

site we designed antibody fusion proteins for therapeutic approaches,

focusing either on optimized presentation or a combined mode of action.

3:30 Refreshment Break

4:00 TIM (T Cell Immunoglobulin and Mucin)-3 as a Potential

Target for Cancer Immunotherapy

Ana Carrizosa Anderson, Ph.D., Assistant Professor, Neurology, Harvard Medical School

TIM-3 marks both “exhausted” CD8+ T cells and regulatory T cells (Treg) present

in solid tumors. TIM-3/PD-1 co-blockade down-modulates Treg suppressor

function in Tim-3+ Treg, restores function to exhausted CD8+ T cells, and is highly

effective in controlling tumor growth. Thus, TIM-3/PD-1 blockade down-modulates

two major mechanisms of immune suppression that are active in tumor-bearing

hosts, namely exhausted CD8+ T cells and Treg.

4:30 Allovectin: In vivo Studies and Potential Synergy with

other Advanced Melanoma Immunotherapeutics

John Doukas, Ph.D., Senior Director, Preclinical Safety and Efficacy, Vical, Inc.

Allovectin® is a cancer immunotherapeutic currently completing

evaluation in a pivotal Phase 3 metastatic melanoma study. Designed

for direct intratumoral administration, it is intended to induce antitumor

immune responses against both treated and distal lesions by stimulating

innate and adaptive immune responses. This presentation will review

Allovectin’s proposed mechanisms of action and potential synergy with

other immunotherapies, drawing supporting data from preclinical and

clinical studies.

5:00 Clinical Update of IL2 Adjunctive Co-Therapy for

Suppression of Solid Tumors with Designer T Cells

Richard P. Junghans, M.D., Professor, Department of Medicine, Boston University School of

Medicine; Roger Williams Medical Center

IL2, an essential adjunct in therapies with tumor-infiltrating lymphocytes, has

not been widely applied in designer T cell interventions, although rationales

for supplementation would seem to bridge both settings. This discrepancy

may reflect the restricted set of investigators with IL2 experience rather than

a biologically motivated choice. Preclinical data establishesthe need for IL2

to eliminate established tumors with dTc, and early clinical data in prostate

cancer targeting may be interpreted similarly.

5:30-6:30 Reception in Exhibit Hall with Poster Viewing

WEDNESDAY , AUGUST 14, 2013

8:55am Chairperson’s Opening Remarks

Emerging Cancer Vaccines

9:00 Challenges in Vaccine Therapy for Hematological

Malignancies

David E. Avigan, M.D., Associate Professor, Medicine, Harvard Medical School; Director,

Hematologic Malignancy/Bone Marrow Transplant Program, Beth Israel Deaconess Medical

Center

We have developed a tumor vaccine in which patient-derived tumor cells

are fused with autologous dendritic cells. We have demonstrated that

vaccination during post-transplant lymphopoietic reconstitution results in the

significant expansion of myeloma-specific T cells. We are now integrating

vaccination with reversing critical elements of tumor-mediated immune

suppression. This includes vaccination in the context of blockade of the

PD-1/PDL-1 pathway.

9:30 Biomarkers Correlative of Clinical Response to Sipuleucel-T

James Trager, Ph.D., Vice President, Research, Dendreon

Sipuleucel-T is an autologous cellular immunotherapy approved in the

United States for the treatment of asymptomatic or minimally symptomatic

metastatic castrate resistant prostate cancer. A variety of biomarkers,

both baseline and pharmacodynamic, are correlative of clinical response to

sipuleucel-T. We will discuss the biological interpretations of these markers

and in particular their implications in understanding the mechanism of action

for sipuleucel-T.

10:00 Partnering Therapeutic Vaccines with Large Pharma

Kevin Heller, Global Lead Oncology; Search, Evaluation and Diligence, Bristol-Myers Squibb

10:30 Refreshment Break in Exhibit Hall with Poster Viewing

11:15 Clinical Results of Pexa-Vec (JX-594): Multi-Mechanistic

Oncolytic Viruses as a Strategy for Cancer Immunotherapy

Anne Moon, Ph.D., Vice President, Product Development, Jennerex

Oncolytic immunotherapy is an emerging therapeutic approach designed

to induce acute tumor debulking as well as chronic suppression of tumor

outgrowth. Pexa-Vec (JX-594) is an oncolytic vaccinia virus engineered for

enhanced cancer targeting and immune stimulation. Recent preclinical and

clinical results demonstrate a multi-pronged MOA, including induction of

tumor-specific immunity, demonstrating the potential for Pexa-Vec to serve

as an active immunotherapy that is “personalized” yet “off-the-shelf.”

11:45 Clinical Update on PROSTVAC, a Therapeutic Vaccine

Candidate for Advanced Prostate Cancer

Alain Delcayre, Ph.D., Vice President, R&D, BN Immunotherapeutics

PROSTVAC® is a candidate cancer vaccine that demonstrated a statistically

significant overall survival benefit while displaying a favorable side effect

profile in patients with asymptomatic-to-minimally-symptomatic metastatic

castrate-resistant prostate cancer in a randomized, placebo-controlled Phase

II trial. A Phase III clinical trial is underway to confirm clinical benefit, as well

as expand our understanding of immune responses to cancer vaccines.

12:15 pm Close of Conference

Sponsoring Pubs

5 ImmunotherapiesCongress.com

The recent approval of BMS’s Yervoy (ipilumumab) and a succession of related programs advancing through clinical trials has generated increased interest

in the development of antibody-based immunomodulators for cancer. Immunomodulatory Therapeutic Antibodies for Cancer will provide updates of

clinical stage programs, and examine how these novel therapeutics influence trial design and the selection of clinical endpoints. Strategies for immune

modulation that are most appropriate for targeting with antibodies will be considered, along with where combination regimens and new therapeutic formats

can be effectively applied.

Inaugural

Immunomodulatory Antibodies for Cancer

Clinical Progress and Challenges in Drug Product Development

August 14-15

WEDNESDAY , AUGUST 14, 2013

1:40 pm Chairperson’s Opening Remarks

»»1:45 Keynote Presentation:

Immune Monitoring on Pre-Surgical Clinical Trials with a Novel

Checkpoint Blockade Agent, Anti-CTLA-4

Padmanee Sharma, M.D., Associate Professor, Genitourinary Medical Oncology, The University

of Texas MD Anderson Cancer Center

Biomarker studies for immunotherapies have typically involved monitoring

immunologic changes within the systemic circulation; however, recent

data indicates that immunological changes within tumor tissues are more

likely to predict clinical responses. We conducted a pre-surgical clinical trial

with anti-CTLA-4 (ipilimumab) in patients with localized bladder cancer, and

identified ICOS as the marker of a subset of effector T cells that is increased

in frequency after anti-CTLA-4 therapy. ICOS+ T cells are being explored

as pharmacodynamic markers for treatment with anti-CTLA-4 and as novel

targets to improve the efficacy of anti-CTLA-4 therapy.

Immune Checkpoint Blockades

2:30 Preliminary Clinical Efficacy and Safety of MK-3475

(Anti-PD-1 Monoclonal Antibody) in Patients with Advanced

Melanoma

Omid Hamid, M.D., Director, Melanoma Center, Angeles Clinic and Research Institute

The programmed death-1 (PD-1) pathway has emerged as an important

tumor-evasion mechanism. When PD-1 and PDL-1 join together, the T cell’s

ability to target the tumor cell is disarmed. Targeting either PD-1 or PDL-1

can stimulate the immune system and enhance T cells’ ability to lyse tumor

cells. Similar to, but distinct from cytotoxic T lymphocyte antigen 4 (CTLA-4)

this pathway hold promise for many solid tumors.

3:00 Sponsored Presentations (Opportunities Available: Contact

Suzanne Carroll at 781-972-5452 or scarroll@healthtech.com for

more information)

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Development of Immunomodulatory PD-1 Antibodies in

Renal Cell Carcinoma

Lauren Harshman, M.D., Assistant Professor, Dana-Farber Cancer Institute

Targeting the immunosuppressive PD-1 pathway is an area of intense

investigation. RCC tumor cells may innately express the ligand of PD-1 or

they may acquire it from adaptive immunity. Expression has been associated

with worse outcomes. Attempts at countering this host immune system

evasion technique are underway with a variety of monoclonal antibodies

against PD-1 and its ligands.

4:45 Anti-PD-1 Antibody Therapy for B-Cell Lymphoma

Sattva S. Neelapu, M.D., Associate Professor, Department of Lymphoma and Myeloma, Division

of Cancer Medicine, The University of Texas MD Anderson Cancer Center

In a phase II trial, the combination of pidilizumab, a humanized anti-PD-1

monoclonal antibody, and rituximab was active and non-toxic in patients with

relapsed follicular lymphoma. Activation of T and NK cells was observed in

both peripheral blood and tumor microenvironment after pidilizumab therapy

and predictors of clinical outcome based on the molecular features of tumorinfiltrating

immune cells at baseline were identified.

5:15 AMP-224, A Fusion Protein with Potential to Modulate

the PD-1 Pathway

Solomon Langermann, Ph.D., CSO, Amplimmune

AMP-224 is the first recombinant B7-DC-Fc fusion protein tested in patients

that binds to and modulates the PD-1 axis through a unique MOA. The

MOA hypothesis for AMP-224 is depletion of PD-1 high expressing T-cells

representing exhausted effector cells. The pharmacodynamic readouts

obtained to date demonstrate that AMP-224 is biologically active in its

target patient population. Data from the trial has been used to establish

hypotheses regarding the characteristics of patients most likely to respond

clinically to AMP-224 treatment.

5:45 Close of Sessions

THURSDAY , AUGUST 15, 2013

Emerging Targets

8:25 am Chairperson’s Opening Remarks

8:30 Immunocytokines: A Novel Potent Class of Armed Antibodies

Catherine Hutchinson, Ph.D., Research Scientist, Philochem, Switzerland

The severe toxicity of recombinant cytokines even at low doses limits

their therapeutic potential, but this can be mitigated by using monoclonal

antibodies to target their delivery. This talk will cover the latest advanced

preclinical and clinical data of the Philogen group, detailing the discovery and

development of armed antibodies against angiogenesis-specific markers,

which are attractive targets relevant to many angioproliferative diseases.

9:00 Mechanism of Action and Progress Update for MGA271:

An Fc-Enhanced mAb Targeting B7-H3 in Solid Tumors

Paul Moore, Ph.D., Vice President, Cell Biology & Immunology, Macrogenics

Characterization of murine monoclonal antibodies generated from cancer

cell and/or stem cell-based immunizations identified a panel targeting the

immunoregulatory protein B7-H3 displaying broad tumor reactivity but

limited binding to normal tissue. Preclinical evaluation of MGA271, an Fcenhanced

anti-B7H3 mAb, revealed strong ADCC activity against a broad

range of tumor cell types, potent antitumor activity in xenograft models

employing human FcR transgenic mice and a favorable safety profile in nonhuman

primate toxicology studies. A phase I/IIa clinical study of MGA271

in patients with B7-H3-positive metastatic or recurrent adenocarcinoma is

currently recruiting patients.

ImmunotherapiesCongress.com 6

9:30 Preclinical Update: Development of a Human Anti-CD27

Monoclonal Antibody as a Potential Cancer Therapy

Lawrence J. Thomas, Ph.D., DABT, CMAR, Senior Director, Preclinical Research and

Development, Celldex Therapeutics, Inc.

Agonist antibodies binding the co-stimulatory molecule CD27 have potent

antitumor activity in murine tumor models through boosting of durable T

cell antitumor immunity. Anti-CD27 antibodies have also been shown to

mediate the direct killing of CD27-expressing tumors. Such preclinical data

supports the therapeutic potential of this anti-CD27 monoclonal antibody as

a cancer immunotherapy.

10:00 Sponsored Presentation (Opportunity Available)

10:15 Refreshment Break in the Exhibit Hall with Poster Viewing

11:00 Targeting CD47-SIRPα Interactions for Potentiating

Antibody Therapy in Cancer

Timo van den Berg, Ph.D., Head, Blood Cell Research, Sanquin Blood Supply Foundation,

The Netherlands

We will present findings demonstrating that interactions between CD47

expressed on cancer cells and the myeloid inhibitory immunoreceptor SIRPα

form a barrier for the antibody-mediated destruction of cancer cells. These

findings identify the CD47-SIRPα interaction as a potential generic target for

improving the efficacy of cancer antibody therapeutics.

11:30 Presentation to be Announced

12:00 Sponsored Presentations (Opportunities Available)

12:30 Luncheon Presentation (Opportunity Available)

or Lunch on Your Own

Clinical Development of

Immunomodulatory Antibodies

1:55 Chairperson’s Opening Remarks

2:00 Clinical Trials Design for Cancer Immune Therapies

Harriet Kluger M.D., Associate Professor, Yale Cancer Center

Clinical development of immune therapies is challenging; standard drug

development paradigms are often not applicable. Modifications are

necessary in regard to dose escalation, management and definition of

toxicities, within-patient dose reduction, and radiographic assessment of

response to therapy. In later stage trials new definitions of study endpoints

are needed. Correlative biomarker studies are complex, and require

assessment of baseline immune function and tumor characteristics.

2:30 Characteristics and Management of Immune-Related

Adverse Effects Associated with Ipilimumab, a New

Immunotherapy for Metastatic Melanoma

Stephanie Andrews, Oncology Nurse Practitioner, Moffitt Cancer Center

Immune-Related Adverse Effects are a new phenomenon related to

advances in the use of the first FDA approved monoclonal antibody

Ipilimumab for metastatic melanoma. These side effects are different

than side effects of traditional cytotoxic regimens. These immunemediated

side effects include enterocolitis, hepatitis, dermatitis,

neuropathy andendocrinopathy.

Bispecific Immunomodulatory Antibodies

3:00 Safety Challenges to Development of Immune System

Activating Antibodies

Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, Global Head, Biologics

Safety Assessment, Pathology & LAR, MedImmune (AstraZeneca Biologics)

Immune system activating antibodies with abilities to harness and enhance

an individual patient’s immune system and target tumors are revolutionizing

the treatment of many deadly cancers. However, many immune-activating

biologics have serious dose-limiting toxicities, including cytokine stormassociated

critical toxicities and serious autoimmune diseases in multiple

key organs that may limit their long-term use. Nonclinical and clinical safety

challenges and risk mitigation opportunities will be discussed in the context

of immune activating antibodies, including bispecific BiTE antibodies.

3:30 Refreshment Break

3:45 MCLA-117: ABiclonics – ENGAGE Bispecific IgG Product

Lead Targeting CLEC12A and CD3 in AML

Lex Bakker, Ph.D., Chief Development Officer, Merus, The Netherlands

MCLA-117, a common light chain T cell-engaging full-length human bispecific

antibody (Biclonics – ENGAGE) was discovered that targets CD3 on T cells

and CLEC12A on acute myeloid leukemia (AML) blasts and leukemic stem

cells. Co-incubation of resting patient T cells and AML cells with MCLA-

117 results in efficient tumor cell lysis. Clinical application of MCLA-117

potentially provides a therapy in AML that more efficiently eradicates the

cancer cells and prevents relapse.

4:15 Bispecific Antibody Targeting CD47 Aiming at Increasing

Phagocytosis of Cancer Cells

Krzysztof Masternak, Ph.D., Head of Biology, Novimmune SA, Switzerland

CD47 is a ubiquitously expressed transmembrane receptor with multiple

functions in cell-to-cell communication. Its interaction with SIRPα expressed

in macrophages and DCs inhibits their phagocytic function. Overexpression

of CD47 in cancer cells is often observed and it is believed to help cancer

cells escape immune surveillance. We have generated bispecific antibodies

(BsAbs) that preferentially neutralize CD47-SIRPα interaction on cancer cells.

4:45 Close of Conference

7 ImmunotherapiesCongress.com

CHI offers comprehensive sponsorship packages which include presentation

opportunities, exhibit space and branding, as well as the use of the pre and

post-show delegate lists. Customizable sponsorship packages allow you to

achieve your objectives before, during, and long after the event. Signing on

early will allow you to maximize exposure to hard-to-reach decision makers!

Agenda Presentations

Showcase your solutions to a guaranteed, highly-targeted audience. Package

includes a 15 or 30-minute podium presentation within the scientific agenda, exhibit

space, on-site branding, and access to cooperative marketing efforts by CHI.

Breakfast & Luncheon Presentations

Opportunity includes a 30-minute podium presentation. Boxed lunches are

delivered into the main session room, which guarantees audience attendance

and participation. A limited number of presentations are available for

sponsorship and they will sell out quickly. Sign on early to secure your talk!

Invitation-Only VIP Dinner/Hospitality Suite

Sponsors will select their top prospects from the conference pre-registration

list for an evening of networking at the hotel or at a choice local venue. CHI

will extend invitations and deliver prospects. Evening will be customized

according to sponsor’s objectives:

• Purely social

• Focus group

• Reception style

• Plated dinner with specific conversation focus

Exhibit

Exhibitors will enjoy facilitated networking opportunities with high-level

conference delegates. Speak face-to-face with prospective clients and

showcase your latest product, service, or solution.

*Inquire about additional branding opportunities!

Looking for aditional ways to drive

leads to your sales team?

CHI can help!

We offer clients numerous options for custom lead generation programs to

address their marketing and sales needs, including:

Custom Lead Generation Programs:

• Targeted campaign promotion to unparalleled database of

800,000+ individuals in the life sciences

• Experienced marketing team promotes campaign, increasing

awareness and leads

Live Webinars:

• Assistance in procuring speakers

• Experienced moderators

• Dedicated operations team to coordinate all efforts

White Papers:

• Industry recognized authors, with vast editorial experience, available

to help write your white paper

CHI also offers market surveys, podcasts, and more!

To customize your participation at this event, please contact:

Suzanne Carroll – Senior Business Development Manager

781-972-5452 | scarroll@healthtech.com

Sponsorship, Exhibit, and Lead Generation Opportunities

Co-Located Event

August 13-15, 2013 • Hilton Boston Back Bay Hotel • Boston, MA

Eighth Annual

Novel Vaccines:

Innovations & Adjuvants

To Advance the Science of Vaccines

Additional registration details

Each registration includes all conference

sessions, posters and exhibits, food

functions, and access to the conference

proceedings link.

Handicapped Equal Access: In accordance

with the ADA, Cambridge Healthtech

Institute is pleased to arrange special

accommodations for attendees with

special needs. All requests for such

assistance must be submitted in writing

to CHI at least 30 days prior to the start

of the meeting.

To view our Substitutions/

Cancellations Policy, go to

http://www.healthtech.com/regdetails

Video and or audio recording of any kind

is prohibited onsite at all CHI events.

Receive a FREE eNewsletter by signing up

at chimediagroup.com

The latest industry news, commentary

and highlights from Bio-IT World

Innovative management in clinical trials

A series of diverse reports designed to

keep life science professionals informed

of the salient trends in pharmaceutical

technology, business, clinical development,

and therapeutic disease markets.

For a detailed list of reports, visit

InsightPharmaReports.com, or contact

Rose LaRaia, rlaraia@healthtech.com,

+1-781-972-5444.

Barnett is a recognized leader in clinical

education, training, and reference guides

for life science professionals involved in

the drug development process. For more

information, visit barnettinternational.com.

Cambridge Healthtech Associates™

(CHA™) leverages its extensive network

and unique collaborative model in

consulting, technology evaluations

and community-based communication

services to help clients in the life

sciences industry commercialize and

penetrate the marketplace to increase

revenue. Visit http://www.chacorporate.com.

Cambridge Healthtech Institute, 250 First Avenue, Suite 300, Needham, MA 02494 • http://www.healthtech.com • Fax: 781-972-5425

Pricing and Registration Information

short courses

Academic, Government,

(Includes access to short courses only) Commercial H ospital-affiliated

Single Short Course $699 $399

Two Short Courses $999 $699

Monday, August 12 • 2:00-5:00pm Wednesday, August 14 • 6:30-9:30pm

Melanoma Biology and Immunotherapies Manufacturing Vaccines: New Approaches, New Technologies

3 Day Pricing • August 13-15 Please Choose Package A or B

(Excludes short courses)

Package A – Novel Vaccines: Innovations & Adjuvants August 13-15

Early Registration Deadline until May 17, 2013 $2049 $1025

Advance Registration Deadline until July 19, 2013 $2199 $1099

Registrations after July 19, 2013 and on-site $2399 $1149

Package B – Emerging Cancer Immunotherapies and Vaccines August 13-14 + Immunomodulatory Antibodies for Cancer August 15-15

Early Registration Deadline until May 17, 2013 $2049 $1025

Advance Registration Deadline until July 19, 2013 $2199 $1099

Registrations after July 19, 2013 and on-site $2399 $1149

1.5 Day Pricing Please Choose Package C or D

(Excludes short courses)

Package C – Emerging Cancer Immunotherapies and Vaccines • August 13-14

Early Registration Deadline until May 17, 2013 $1399 $649

Advance Registration Deadline until July 19, 2013 $1599 $729

Registrations after July 19, 2013 and on-site $1799 $799

Package D – Immunomodulatory Antibodies for Cancer • August 14-15

Early Registration Deadline until May 17, 2013 $1399 $649

Advance Registration Deadline until July 19, 2013 $1599 $729

Registrations after July 19, 2013 and on-site $1799 $799

Conference Discounts

Poster Submission-Discount ($50 Off)

Poster abstracts are due by July 19, 2013. Once your registration has been fully processed, we will send an email containing a unique link allowing

you to submit your poster abstract. If you do not receive your link within 5 business days, please contact jring@healthtech.com. *CHI reserves the

right to publish your poster title and abstract in various marketing materials and products.

Alumni Discount-Discount (SAVE 20%)

Cambridge Healthtech Institute (CHI) appreciates your past participation at the ImVacS & the Immunotherapies Congress. As a result of the great

loyalty you have shown us, we are pleased to extend to you the exclusive opportunity to save an additional 20% off the registration rate.

REGI STER 3 –

4th IS FREE: Individuals must register for the same conference or conference combination and submit completed registration form together for

discount to apply.

Additional discounts are available for multiple attendees from the same organization. For more information on group rates contact

David Cunningham at +1-781-972-5472

If you are unable to attend but would like to purchase the ImVacS & the Immunotherapies Congress CD for $750 (plus shipping),

please visit ImVacS.com. Massachusetts delivery will include sales tax.

How to Register: ImmunotherapiesCongress.com

reg@healthtech.com • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288

Please use keycode

IMT F

when registering!

(Alumni and Register 3 – 4th is free discounts cannot be combined)

Immuno The

Congress

herapies

August 13-15, 2013

Boston, MA

 

Immune Checkpoint Blockades

Keynote Presentation: Immune Monitoring on Pre-Surgical Clinical Trials with a Novel Checkpoint Blockade Agent, Anti-CTLA-4

Padmanee Sharma, M.D., Associate Professor, Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center

 

Biomarker studies for immunotherapies have typically involved monitoring immunologic changes within the systemic circulation; however, recent data indicates that immunological changes within tumor tissues are more likely to predict clinical responses. We conducted a pre-surgical clinical trial with anti-CTLA-4 (ipilimumab) in patients with localized bladder cancer, and identified ICOS as the marker of a subset of effector T cells that is increased in frequency after anti-CTLA-4 therapy. ICOS+ T cells are being explored as pharmacodynamic markers for treatment with anti-CTLA-4 and as novel targets to improve the efficacy of anti-CTLA-4 therapy.

 

Preliminary Clinical Efficacy and Safety of MK-3475 (Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Melanoma

Omid Hamid, M.D., Director, Melanoma Center, Angeles Clinic and Research Institute

 

Sponsored Presentations (Opportunities Available: Contact Jason Gerardi at 781-972-5452 or jgerardi@healthtech.com for more information)

 

Development of Immunomodulatory PD-1 Antibodies in Renal Cell Carcinoma

Lauren Harshman, M.D., Assistant Professor, Dana-Farber Cancer Institute

 

Anti-PD-1 Antibody Therapy for B-Cell Lymphoma

Sattva S. Neelapu, M.D., Associate Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

 

AMP-224, A Fusion Protein with Potential to Modulate the PD-1 Pathway

Solomon Langermann, Ph.D., CSO, Amplimmune

 

Emerging Targets

 

Immunocytokines: A Novel Potent Class of Armed Antibodies

Catherine Hutchinson, Ph.D., Research Scientist, Philochem, Switzerland

 

Mechanism of Action and Progress Update for MGA271: An Fc-Enhanced mAb Targeting B7-H3 in Solid Tumors

Paul Moore, Ph.D., Vice President, Cell Biology & Immunology, Macrogenics

 

Preclinical Update: Development of a Human Anti-CD27 Monoclonal Antibody as a Potential Cancer Therapy

Lawrence J. Thomas, Ph.D., DABT, CMAR, Senior Director, Preclinical Research and Development, Celldex Therapeutics, Inc.

 

Targeting CD47-SIRPa Interactions for Potentiating Antibody Therapy in Cancer

Timo van den Berg, Ph.D., Head, Blood Cell Research, Sanquin Blood Supply Foundation, The Netherlands

 

Clinical Development of Immunomodulatory Antibodies

 

Clinical Trials Design for Cancer Immune Therapies

Harriet Kluger M.D., Associate Professor, Yale Cancer Center

 

Characteristics and Management of Immune-Related Adverse Effects Associated with Ipilimumab, a New Immunotherapy for Metastatic Melanoma

Stephanie Andrews, Oncology Nurse Practitioner, Moffitt Cancer Center

 

Bispecific Immunomodulatory Antibodies

 

Safety Challenges to Development of Immune System Activating Antibodies

Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, Global Head, Biologics Safety Assessment, Pathology & LAR, MedImmune (AstraZeneca Biologics)

 

MCLA-117: ABiclonics – ENGAGE Bispecific IgG Product Lead Targeting CLEC12A and CD3 in AML

Lex Bakker, Ph.D., Chief Development Officer, Merus, The Netherlands

 

Bispecific Antibody Targeting CD47 Aiming at Increasing Phagocytosis of Cancer Cells

Krzysztof Masternak, Ph.D., Head of Biology, Novimmune SA, Switzerland

 

View FInal Agenda | Pricing & Registration Details

 

Sponsorship & Exhibit Information

 

CHI offers comprehensive sponsorship packages which include presentation opportunities, exhibit space and branding, as well as the use of the pre and post show delegate list. Sponsorship allows you to achieve your objectives before, during, and long after the event. Any sponsorship can be customized to meet your company’s needs and budget. Signing on earlier will allow you to maximize exposure to hard-to-reach decision makers.

 

For sponsor & exhibitor information, please contact:

 

Jason Gerardi- Manager, Business Development

781-972-5452 | jgerardi@healthtech.com

 

ImmunotherapiesCongress.com/Immunomodulatory-Antibodies-Cancer

 

Cambridge Healthtech Institute, 250 First Avenue, Suite 300,  Needham, MA 02494 healthtech.com

http://www.immunotherapiescongress.com/Conferences_Overview.aspx?id=124174 

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