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Posts Tagged ‘Memorial Sloan–Kettering Cancer Center’


Reporter: Aviva Lev-Ari, PhD, RN

 

Researchers Report on Mutational Patterns in Adenoid Cystic Carcinoma

May 20, 2013

NEW YORK (GenomeWeb News) – A Memorial Sloan-Kettering Cancer Center-led team has taken an exome- and genome-sequencing centered look at the mutations that may be found in the salivary gland cancer adenoid cystic carcinoma, or ACC.

As they reported in Nature Genetics online yesterday, the researchers did exome or genome sequencing on five-dozen matched ACC tumor and normal pairs.

Their analysis unearthed relatively few glitches in each tumor’s protein-coding sequences. But the group found suspicious mutations to several main pathways, including some — such as the PI3-kinase, fibroblast growth factor, and insulin-like growth factor-containing pathway — that may make promising treatment targets.

“Our discovery of genomic alterations in targetable pathways suggests potential avenues for novel treatments to address a typically chemoresistant malignancy,” corresponding author Timothy Chan, an oncology researcher at Memorial Sloan-Kettering, and his colleagues wrote, noting that “[v]erified ACC cell lines are needed to further substantiate the clinical usefulness of the mutations identified here.”

A few genetic glitches have been linked to ACC in the past, the team noted, including a fusion between the transcription factor genes MYB and NFIB. The tumors are also notorious for having higher-than-usual expression of certain genes, such as the epidermal growth factors. Even so, there is still a ways to go in characterizing and treating the aggressive cancer.

To get a better sense of the nature and frequency of mutations involved in ACC, the researchers used Illumina’s HiSeq2000 to do exome sequencing on 55 matched ACC and normal samples, as well as whole-genome sequencing on five more tumor-normal pairs.

For the exome sequencing experiments, they used Agilent SureSelect kits to capture protein-coding portions of the genome prior to sequencing. In the subsequent analyses, meanwhile, the group relied on Life Tehnologies’ SOLiD and Illumina’s MiSeq platforms to verify apparent single nucleotide glitches and small insertions and deletions.

With 106-fold coverage of the exomes, on average, and 37-fold average coverage of the genomes, the group was able to track down a mean of almost two-dozen somatic coding alterations per tumor.

When they used an algorithm called CHASM to distinguish between driver and passenger mutations in a set of 710 validated non-synonymous mutations, the researchers saw an over-representation of apparent driver mutations affecting genes known for processes ranging from chromatin regulation and DNA damage response to signaling and metabolism.

For instance, more than one-third of the tumors harbored mutations to chromatin regulators or chromatin state modifying genes such as SMARCA2, CREBBP, and KDM6A. Similarly, the researchers tracked down multiple mutations to genes coding for enzymes involved in adding or removing methylation and acetylation marks to histones.

Glitches to DNA damage response pathways also turned up in multiple tumors, they reported, as did mutations involving genes from the FGF-IGF-PI3K and other signaling pathways.

Some 57 percent of the tumors tested contained the MYB-NFIB fusion that had been implicated in ACC previously. But the new analysis also turned up mutations affecting genes that interact with MYB and in the NFIB gene itself, pointing to widespread — and perhaps complex — involvement for the two transcription factors in ACC.

“Our data highlight MYB as an active oncogenic partner in fusion transcripts in ACC,” the study’s authors said, “but also suggest a separate role for NFIB, given the presence of mutations specific to this gene.”

Going forward, the group hopes to see further analyses on alterations uncovered in the current study, particularly those falling in pathways that might be prone to clinical interventions.

“[O]ur data provide insights into the genetic framework underlying ACC oncogenesis,” the researchers concluded, “and establish a foundation for identifying new therapeutic strategies.”

 

 

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Discovery on Target: Industry’s Preeminent Event on Novel Drug Targets 

Reporter: Aviva Lev-Ari, PhD, RN

 

ABOUT THIS CONFERENCE

Cambridge Healthtech Institute’s tenth annual conference on Functional Genomics Screening Strategies will cover the latest in the use of RNA interference (RNAi) screens, combination (RNAi and small molecule) screens, chemical genomics and phenotypic screens, for identifying and validating new drug targets and exploring unknown cellular pathways. The first half of the conference will focus on the design and use of RNAi screens, while the second half will explore the use of chemical genomics screens, microRNA (miRNA) and long non-coding RNA (LncRNA) screens and the transition into advanced cellular models such as, 3D cell cultures, co-cultures and stem cells that will launch the next-generation of functional screens. Screening experts from pharma/biotech as well as from academic and government labs will share their experiences leveraging the utility of such diverse screening platforms and models for a wide range of applications.

SUGGESTED EVENT PACKAGE:

September 23: Setting Up Effective RNAi Screens: Getting From Design to Data Short Course
September 24 – 25: Functional Genomic Screening Strategies Conference Part One
September 25: Setting Up Effective Functional Screens Using 3D Cell Cultures Dinner Short Course
September 25 – 26: Functional Genomic Screening Strategies Conference Part Two

 

WHERE AND HOW TO APPLY SIRNA AND SHRNA SCREENS

Comparative Analysis of Arrayed RNAi Screening Performance of siRNA versus shRNA at Genome-Scale

Hakim Djaballah, Ph.D., Director, HTS Core Facility, Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center

 

RNAi Screening: Strategies, Examples and Outcomes

David Root, Ph.D., Director, RNAi Platform and Project Leader, The RNAi Consortium, The Broad Institute of MIT and Harvard

 

Swimming in the Deep End – Sources Leading to a False Sense of Security in RNAi Screen Data

Scott Martin, Ph.D., Team Leader, RNAi Screening, NIH Chemical Genomics Center, NIH Center for Translational Therapeutics, National Institutes for Health

 

Rebuilding the RNAi Screen

Eugen Buehler, Ph.D., Group Leader, Informatics, National Center for Advancing Translational Sciences, National Institutes of Health

 

Genetic Strategies for Investigating Host-Virus Interactions

Abraham Brass, M.D., Ph.D., Assistant Professor, Department of Microbiology and Physiology Systems, University of Massachusetts Medical School

 

PANEL DISCUSSION: Advanced RNAi Screening: Strengths, Caveats and Pitfalls at Reaching the 14-Year Milestone

Moderator: Christophe Echeverri, Ph.D., CEO & CSO, Cenix BioScience USA, Inc.

Panelists:

Caroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility, Harvard Medical School

David Root, Ph.D., Director, RNAi Platform and Project Leader, The Broad Institute

Hakim Djaballah, Ph.D., Director, HTS Core Facility, Memorial Sloan Kettering Cancer Center

Scott Martin, Ph.D., Team Leader, RNAi Screening, NIH Chemical Genomics Center

 

 

EXPLORING DIVERSE APPLICATIONS

RNAi Screening to Enable Translational R&D For Oncology and Immuno-Oncology Target Discovery

Namjin Chung, Ph.D., Senior Research Investigator, Applied Genomics, Bristol-Myers Squibb Co.

 

Target Identification and Validation of Novel Ion Channels in Cancer

Alex Gaither, Ph.D., Research Investigator II, Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research

 

Cell-Based Functional Profiling of Lipid-Traits and Cardiovascular Disease

Heiko Runz, M.D., Group Leader, Molecular Metabolic Disease Unit, Institute of Human Genetics; Group Leader, University of Heidelberg

 

Use of Functional Genomics to Identify Patients at High Risk for Recurrence of Hepatitis C Following Liver Transplantation

Robert Carithers, M.D., Professor of Medicine, Director, Liver Care Line; Medical Director, Liver Transplant Program, University of Washington Medical Center

CellectaPooled RNAi Genetic Screening to Identify Functional Genes and Novel Drug Targets

Paul Diehl, Director, Business Development, Cellecta, Inc.

 

TECHNOLOGY PANEL: Tools for Next-Generation Functional Genomics Screens

Moderator: Christophe Echeverri, Ph.D., CEO & CSO, Cenix BioScience USA, Inc.

This panel will bring together 4-5 technical experts from leading technology and service companies to discuss screening trends and improvements in assay platforms and reagents that users can expect to see in the near future.

(Opportunities Available for Sponsoring Panelists)

 

 

COMBINING USE OF RNAI AND OTHER TECHNOLOGIES

siRNA Screening and RNA-seq for Identification of Targets for the Treatment of Alzheimer’s Disease

Paul Kassner, Ph.D., Director, Research, Amgen, Inc.

 

Fusing RNAi Screening and Gene Expression Analyses to Reveal Pathway Responses

Alexander Bishop, Ph.D., Assistant Professor, Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio

http://www.discoveryontarget.com/RNAi-Screens-Functional-Genomics/ 

 

 

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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.

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The latest industry news, commentary

and highlights from Bio-IT World

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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

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the drug development process. For more

information, visit barnettinternational.com.

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(CHA™) leverages its extensive network

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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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