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Archive for the ‘Immunotherapy’ Category


Imaging (ECHO) marker that would identify early cardiotoxic effects: The impact of high-dose immunosuppression for ICI myocarditis Cardiac Echo Tracks Checkpoint Inhibitor Damage – Predicting cardiac injury before EF falls

Reporter: Aviva Lev-Ari, PhD, RN

The present study is the first to use Global longitudinal strain (GLS) specifically to identify immune checkpoint inhibitors (ICI) myocarditis, Abraham and Aras noted.

The study compared 101 ICI myocarditis cases from a multicenter international registry (30 with serial GLS) against a random sample of 92 ICI users at Neilan’s institution who did not present with myocarditis (14 with serial GLS) during a study period from 2013 through 2019.

Despite not propensity-matching these patients, the investigators ended up with two groups with similar age (around 65), sex (>60% men), and cancer type (most commonly melanoma and lung cancer).

Before ICI therapy, GLS was similar between groups (20.3% among cases and 20.6% among controls, P=0.60).

Patients who had myocarditis still had a normal ejection fraction in 60% of cases.

One major limitation of the study was that serial echocardiograms had not been routinely performed on people with myocarditis. “[T]hus, it was not possible to determine if the GLS decrease occurred prior to the development of myocarditis,” Neilan and colleagues acknowledged.

Furthermore, 97% of ICI myocarditis cases presented with elevated troponin levels, so it’s “unclear if GLS assessment has incremental value to such readily available biomarkers,” the editorialists pointed out.

“Additional work is needed to test if the GLS decrease occurs prior to the development of clinical myocarditis, can provide an early method of detection, and whether tailoring immunosuppressive therapy based on the measurement of GLS at presentation with myocarditis may be of value,” the authors said.

 

SOURCES

 

  • Cardiac Echo Tracks Checkpoint Inhibitor Damage

https://www.medpagetoday.com/cardiology/chf/84682?xid=nl_mpt_DHE_2020-02-04&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Top%20Cat%20HeC%20%202020-02-04&utm_term=NL_Daily_DHE_dual-gmail-definition

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New Type of Killer T-Cell

Reporter: Irina Robu, PhD

Scientists at Cardiff University have revealed a new type of killer T-cell which offers hope of a “one-size-fits-all” cancer therapy. Cancer-targeting via MR1-restricted T-cells is a thrilling new frontier, it increases the prospect of a ‘one-size-fits-all’ cancer treatment; a single type of T-cell that could be proficient of destroying numerous different types of cancers across the population.

T-cell therapies for cancer anywhere immune cells are removed, modified and returned to the patient’s blood to seek and destroy cancer cells – are the latest paradigm in cancer treatments. The most extensively-used therapy, known as CAR-T (Chimeric Antigen Receptor T-cell therapy) encompasses genetic modification of patient’s autologous T-cells to express a CAR specific for a tumor antigen, subsequent by ex vivo cell expansion and re-infusion back to the patient. The therapy is personalized to each patient, but targets only a few types of cancers.

Currently, Cardiff academics discovered T-cells equipped with a new type of T-cell receptor (TCR) which recognizes and kills most human cancer types, while ignoring healthy cells. This new TCR distinguishes when a molecule is present on the surface of a wide range of cancer cells and is able to distinguish between cancerous and healthy cells. Normal T-cells scans the surface of other cells to find anomalies and eliminate cancerous cells, yet ignores cells that contain only normal proteins.

The researchers at Cardiff was published in Nature Immunology, labels a unique TCR that can identify various types of cancer via a single HLA-like molecule called MR1 which varies in the human population. HLA differs extensively between individuals, which has previously prevented scientists from creating a single T-cell-based treatment that targets most cancers in all people. To investigate the therapeutic potential of these cells in vivo, the investigators injected T-cells able to identify MR1 into mice bearing human cancer and with a human immune system.

The Cardiff group were able to demonstrate that T-cells of melanoma patients modified to express this new TCR could destroy not only the patient’s own cancer cells, but also other patients’ cancer cells in the laboratory, irrespective of the patient’s HLA type. Experiments are under way to regulate the exact molecular mechanism by which the new TCR differentiates between healthy cells and cancer.

Source

https://www.eurekalert.org/pub_releases/2020-01/cu-don012020.php

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Effective humoral immune responses to infection and immunization are defined by high-affinity antibodies generated as a result of B cell differentiation and selection that occurs within germinal centers (GC). Within the GC, B cells undergo affinity maturation, an iterative and competitive process wherein B cells mutate their immunoglobulin genes (somatic hypermutation) and undergo clonal selection by competing for T cell help. Balancing the decision to remain within the GC and continue participating in affinity maturation or to exit the GC as a plasma cell (PC) or memory B cell (MBC) is critical for achieving optimal antibody avidity, antibody quantity, and establishing immunological memory in response to immunization or infection. Humoral immune responses during chronic infections are often dysregulated and characterized by hypergammaglobulinemia, decreased affinity maturation, and delayed development of neutralizing antibodies. Previous studies have suggested that poor antibody quality is in part due to deletion of B cells prior to establishment of the GC response.

 

In fact the impact of chronic infections on B cell fate decisions in the GC remains poorly understood. To address this question, researchers used single-cell transcriptional profiling of virus-specific GC B cells to test the hypothesis that chronic viral infection disrupted GC B cell fate decisions leading to suboptimal humoral immunity. These studies revealed a critical GC differentiation checkpoint that is disrupted by chronic infection, specifically at the point of dark zone re-entry. During chronic viral infection, virus-specific GC B cells were shunted towards terminal plasma cell (PC) or memory B cell (MBC) fates at the expense of continued participation in the GC. Early GC exit was associated with decreased B cell mutational burden and antibody quality. Persisting antigen and inflammation independently drove facets of dysregulation, with a key role for inflammation in directing premature terminal GC B cell differentiation and GC exit. Thus, the present research defines GC defects during chronic viral infection and identify a critical GC checkpoint that is short-circuited, preventing optimal maturation of humoral immunity.

 

Together, these studies identify a key GC B cell differentiation checkpoint that is dysregulated during chronic infection. Further, it was found that the chronic inflammatory environment, rather than persistent antigen, is sufficient to drive altered GC B cell differentiation during chronic infection even against unrelated antigens. However, the data also indicate that inflammatory circuits are likely linked to perception of antigen stimulation. Nevertheless, this study reveals a B cell-intrinsic program of transcriptional skewing in chronic viral infection that results in shunting out of the cyclic GC B cell process and early GC exit with consequences for antibody quality and hypergammaglobulinemia. These findings have implications for vaccination in individuals with pre-existing chronic infections where antibody responses are often ineffective and suggest that modulation of inflammatory pathways may be therapeutically useful to overcome impaired humoral immunity and foster affinity maturation during chronic viral infections.

 

References:

 

https://www.biorxiv.org/content/10.1101/849844v1

 

https://www.ncbi.nlm.nih.gov/pubmed/25656706

 

https://www.ncbi.nlm.nih.gov/pubmed/27653600

 

https://www.ncbi.nlm.nih.gov/pubmed/26912368

 

https://www.ncbi.nlm.nih.gov/pubmed/26799208

 

https://www.ncbi.nlm.nih.gov/pubmed/23001146

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

One of the most contagious diseases known to humankind, measles killed an average of 2.6 million people each year before a vaccine was developed, according to the World Health Organization. Widespread vaccination has slashed the death toll. However, lack of access to vaccination and refusal to get vaccinated means measles still infects more than 7 million people and kills more than 100,000 each year worldwide as reported by WHO. The cases are on the rise, tripling in early 2019 and some experience well-known long-term consequences, including brain damage and vision and hearing loss. Previous epidemiological research into immune amnesia suggests that death rates attributed to measles could be even higher, accounting for as much as 50 percent of all childhood mortality.

 

Over the last decade, evidence has mounted that the measles vaccine protects in two ways. It prevents the well-known acute illness with spots and fever and also appears to protect from other infections over the long term by giving general boost to the immune system. The measles virus can impair the body’s immune memory, causing so-called immune amnesia. By protecting against measles infection, the vaccine prevents the body from losing or “forgetting” its immune memory and preserves its resistance to other infections. Researchers showed that the measles virus wipes out 11% to 73% of the different antibodies that protect against viral and bacterial strains a person was previously immune to like from influenza to herpes virus to bacteria that cause pneumonia and skin infections.

 

This study at Harvard Medical School and their collaborators is the first to measure the immune damage caused by the virus and underscores the value of preventing measles infection through vaccination. The discovery that measles depletes people’s antibody repertoires, partially obliterating immune memory to most previously encountered pathogens, supports the immune amnesia hypothesis. It was found that those who survive measles gradually regain their previous immunity to other viruses and bacteria as they get re-exposed to them. But because this process may take months to years, people remain vulnerable in the meantime to serious complications of those infections and thus booster shots of routine vaccines may be required.

 

VirScan detects antiviral and antibacterial antibodies in the blood that result from current or past encounters with viruses and bacteria, giving an overall snapshot of the immune system. Researchers gathered blood samples from unvaccinated children during a 2013 measles outbreak in the Netherlands and used VirScan to measure antibodies before and two months after infection in 77 children who’d contracted the disease. The researchers also compared the measurements to those of 115 uninfected children and adults. Researchers found a striking drop in antibodies from other pathogens in the measles-infected children that clearly suggested a direct effect on the immune system resembling measles-induced immune amnesia.

 

Further tests revealed that severe measles infection reduced people’s overall immunity more than mild infection. This could be particularly problematic for certain categories of children and adults, the researchers said. The present study observed the effects in previously healthy children only. But, measles is known to hit malnourished children much harder, the degree of immune amnesia and its effects could be even more severe in less healthy populations. Inoculation with the MMR (measles, mumps, rubella) vaccine did not impair children’s overall immunity. The results align with decades of research. Ensuring widespread vaccination against measles would not only help prevent the expected 120,000 deaths that will be directly attributed to measles this year alone, but could also avert potentially hundreds of thousands of additional deaths attributable to the lasting damage to the immune system.

 

References:

 

https://hms.harvard.edu/news/inside-immune-amnesia?utm_source=Silverpop

 

https://science.sciencemag.org/content/366/6465/599

 

www.who.int/immunization/newsroom/measles-data-2019/en/

 

https://www.ncbi.nlm.nih.gov/pubmed/20636817

 

https://www.ncbi.nlm.nih.gov/pubmed/27157064

 

https://www.ncbi.nlm.nih.gov/pubmed/30797735

 

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DISCOVER BRIGHAM | NOVEMBER 7, 2019, 10AM – 6PM

#DISCOVERBRIGHAM

@pharma_BI

@AVIVA1950

 Aviva Lev-Ari, PhD, RN will be attending and will cover presentations in real time

ABOUT BRIGHAM RESEARCH

Discover Brigham is hosted by the Brigham Research Institute (BRI), under the umbrella of Brigham Health. Launched in 2005, the BRI’s mission is to accelerate discoveries that improve human health by bridging the gaps between science, communication and funding. The BRI’s resources help to foster groundbreaking interdepartmental and interdisciplinary research. They provide a voice for the research community and raise the profile of Brigham Research.

Speakers

http://www.discoverbrigham.org/speakers/

 

AGENDA

http://www.discoverbrigham.org/agenda/

ASK A QUESTION WITH SLI.DO!

DO YOU WANT TO SUBMIT A QUESTION TO A SPEAKER OF A SESSION? YOU CAN DO IT THROUGH SLI.DO!

2. ENTER THE EVENT CODE: DB19. THEN HIT JOIN!
3. PICK THE SESSION YOU WANT TO ASK A QUESTION. THEN ASK YOUR QUESTION!
4. YOUR QUESTION WILL BE REVIEWED AND MAY BE FORWARDED TO THE CHAIR TO ASK THE SPEAKER(S).

IT WORKS ON ANY DEVICE, YOU DO NOT NEED TO INSTALL ANYTHING!

 

Registration will open at 9:00 AM and will be located throughout the hospital including

  • Schlager Atrium (formerly known as Cabot Atrium, 45 Francis Street Lobby),
  • Schuster Lobby (75 Francis Street Entrance),
  • Shapiro Cardiovascular Center (70 Francis Street Entrance), and the
  • Hale Building for Transformative Medicine (HBTM) 1st Floor (60 Fenwood Road).

 

Click here for directions to these locations.  

NAVIGATING THE BRIGHAM IS EASIER THAN EVER

Need directions to a clinic, conference room, public space, or help assisting someone who looks lost?

Try our browser-based wayfinding tool and mobile app, BWH Maps,
which provides real-time location tracking and directions in the hospital.

Look for BWH Maps on the Apple App Store and Google Play Store,
or visit maps.brighamandwomens.org.

REGISTRATION LOCATIONS

Please visit one of the registration desks listed below to check-in, receive your badge, and collect any necessary materials. Registration will begin starting at 9:00 AM at each of the locations below.

 

Click on each location below for directions. 

  • SCHLAGER ATRIUM, FORMERLY KNOWN AS CABOT ATRIUM (45 FRANCIS ST. LOBBY)
  • SCHUSTER LOBBY (75 FRANCIS ST. LOBBY)
  • CARL J. AND RUTH SHAPIRO
    CARDIOVASCULAR CENTER
  • HALE BUILDING FOR
    TRANSFORMATIVE MEDICINE

SESSION LOCATIONS

Below you will find directions to each of the session locations.

MARSHALL A. WOLF CONFERENCE ROOM

HALE BUILDING FOR TRANSFORMATIVE MEDICINE

SESSION ROOM

FROM 60 FENWOOD ROAD:
Enter at 60 Fenwood Rd lobby entrance.

STAIRS:
Take the lobby staircase to the 2nd floor. Walk past the balcony overlooking the atrium and take the stairs on the left (Stair 2) to the 3rd floor. Once on the 3rd floor, exit the stairwell and take a right. The room is to your right through the double glass door, straight ahead.

ELEVATOR:
Take S Elevator to 3rd floor. Take a right out of the elevator. The room is past the stairwell, on your right through the double glass doors.

HALE VTC 02006B CONFERENCE ROOM

HALE BUILDING FOR TRANSFORMATIVE MEDICINE

OVERFLOW ROOM FOR MARSHALL A. WOLF CONFERENCE ROOM

FROM 60 FENWOOD ROAD:
Enter at 60 Fenwood Rd lobby entrance.

STAIRS:
Take the lobby staircase to the 2nd floor. The conference room will be on your right near the display monitor.

ELEVATOR:
Enter at 60 Fenwood Rd main entrance and take the S Elevator to the 2nd floor. Once you exit the elevator, take a right and walk past the balcony overlooking the atrium and the conference room will be straight ahead near the display monitor.

ZINNER BREAKOUT ROOM

CARL J. AND RUTH SHAPIRO CARDIOVASCULAR CENTER

SESSION ROOM

FROM 70 FRANCIS STREET:
The Zinner Breakout Room is located in the Carl J. and Ruth Shapiro Cardiovascular Center at 70 Francis Street, Boston, MA. Upon entering the building at the street level, walk straight towards the escalators in the rear of the building. The Zinner Conference Center is located on your right; the Breakout room is through the large doors on the left.

ZINNER BOARDROOM

CARL J. AND RUTH SHAPIRO CARDIOVASCULAR CENTER

OVERFLOW ROOM FOR ZINNER BREAKOUT ROOM

FROM 70 FRANCIS STREET:
The Zinner Boardroom is located in the Carl J. and Ruth Shapiro Cardiovascular Center at 70 Francis Street, Boston, MA. Upon entering the building at the street level, walk straight towards the escalator, keeping to the left side of the building. The Conference Center is located on your right; the Boardroom is through the large doors on the back wall.

BORNSTEIN FAMILY AMPHITHEATER

MAIN PIKE, 45 FRANCIS STREET LOBBY

SESSION ROOM

FROM 45 FRANCIS STREET:
Coming from 45 Francis Street lobby, walk towards the Main Pike (2nd floor hallway). Then take left on the Main Pike, 2nd door on right.

AGENDA

10:00 AM – 11:00 AM

Opening remarks

Elizabeth G. Nabel, MD, President Brigham Health, Prof. Medicine @HarvardMed

  • 8th event since 2012
  • show casing amazing research
  • Open to the Public: Patients, Families to educate
  • 90 Posters
  • Health equity perspective as DNA of the Brigham
  • Learn a new idea, meet someone new, create a new idea

Keynote Introduction

David Bates, MD @DBatesSafety

KEYNOTE

KYU RHEE, MD, MPP, VICE PRESIDENT & CHIEF HEALTH OFFICER, IBM CORPORATION & IBM WATSON HEALTH

MAIN PIKE, 45 FRANCIS STREET LOBBY
  • Partnership BWH & IBM WATSON
  • Big data of claims from providers to payers
  • Waiting rookms in Healthcare delivery
  • Government: ACA
  • AI Spring is here, no more Winter for AI
  • Health disparities, salaries, sexual orientation – improving health of populations
  • Science & Security
  • Red Hat – data security – big data statoscope
  • Healthcare Culture & Technology Culture: IBM & Amazon hire healthcare professionals
  • Cost: Burnout, managing population health,
  • Reduce physicians burnout
  • Culture Tech – Competition by IBM’s Project Debater

11:15 AM – 12:50 PM

1:00 – 1:50 PM

FROM 70 FRANCIS STREET:
The Zinner Breakout Room is located in the Carl J. and Ruth Shapiro Cardiovascular Center at 70 Francis Street, Boston, MA. Upon entering the building at the street level, walk straight towards the escalators in the rear of the building. The Zinner Conference Center is located on your right; the Breakout room is through the large doors on the left.

Aaron Goldman
HaeLin Jang
Greog K. Gerber
  • Microbiome – Bacteria and Fungus therapies – computational tools for applications on microbiome
  • Diagnostics
  • Microbiome in early childhood
  • temporal variability during adulthood
  • host disease bacteriptherapeutics: C-Diff
  • Bugs as drugs
  • Gnotobiotic mice model for c-Diff in mice
  • MDSINE – Microbial dynamin model interaction model
  • cancer microbiome: Bacteria causing cancer, cancer changing the bacteria environment

 

Jeff Karp BENG PhD @MrJeffKarp

  • tissue based patch to seal open foramane ovale. Project remained in Academic settings however
  • GLUE component was commercialized
  • bioinspiration from living organs in Nature, slugs
  1. Viscose secretions
  2. Hydrophobic secretions and snails and sand castle worms

1:00 – 1:50 PM

Lina Matta, PharmD
Joji Suzuki, MD
Lisa WIchmann
Kevin Elias, MD
Daiva Braunfelds,MBA HPH
Elizabeth Cullen, MS

2:00 – 2:50 PM

3:00 – 3:50 PM

David Levin
Christopher baugh
Kathryn Britton
Joanne Feinberg Goldstein
Amrita Shahani
If patient meets criteria for Home Hospital : all services are sent home.
2016 – Pilot randomized controlled trial
2017-2018 – Repeat of Pilot on larger population
2018 – High-volume single arm innovation services
2019 – studies within home hospital wtth sensors at home
2020 – continue
Operation and Research lead to innovations

Anna Krichevsky, PhD HMS Initiative for RNA Medicine

  • paradox of organismal complexity and # protein encoding genes
  • Human genome, 70% Transcriptome Non-coding RNA only 2% encode proteins
  • Non-coding RNA small, long, multifunctional
  • biogenesis of offending RNAs can be drugged
  • RNA novel therapies: RNA as a Drug,
  • Indications: Brain Tumors and AD: MicroRNA (miRNA)the smallest Glioblastoma – only 4 drugs FDA approved in 25 years miRNA – 10b inhibition kills gliomacells miR-132 most neuroprotective RNA
  • Cardiovascular

Paul Anderson, MD, PhD

  • ALS and FTD – Fronto Temporal Dimensia
  • Riluzone 1970 – anti Anti-glutamateric
  • Edarabone 2017 drugs approved – anti-oxidative
  • Andogenesis role in Motor protection from Stress Cytoplasmatic tRNA – ANdiogenin (ANG) production
  • 20 amino acids
  • 5″-tiRNAs assemble G-quadruples – G4
  • point mutationin ANG (mANG) reduce its RNanase
  • G4-containing DNA analogs of 5″-tiRNA (Ala)

Marc Feinberg, MD

  • Cardiovascular: CAD, Insulin resistence – Vascular inflammation
  • Impaired angiogenesis: post MI repair CHF
  • MiRNA therapeutics for Atherosclerosis – miR-181b: Aortic ECs Athero (mice) CAD (Human)
  • miRNA _ Liposomes injected in the vessel wall – reduction of inflammation in vessel – microRNA Group
  • monocyte – How can we increase or amintain mir-181b expression in endothelial cells?
  • LncRNA Therapeutics for vascular Senescence and Atherosclerosis – no effect on leucocyte accumulation no difference in inflammation
  • DNA-dependent protein kinase (DNA-PK)
  • Does Loss SNHG12 triggers vascular senescence in the vessel wall

 

Clemens Scherzer, MD

  • The Protein RNA Brain
  • Dopamin p
  • BRAINCODE: 64% RNA: mRNA, ncRNA,
  • cell-type-spacific putative enhancer RNAs (eRNAs)
  • eRNAs indicate active genetic switches
  • central dogma in Biology: DNA, non-coding RNA, Protein
  • Top 10 Markers
  • Neuropsychiatric Disease: Parkinson: How do genetic variants function in specific brain cells: neurons, microglia, astrocytes
  • genetic variants of neuropsychiatric diseases over-localize to active eRNA sites in dopamine neurons
  • enhancers RNA – ADHD,
  • enhacers RNA – schizoprania, bipolar, addiction – antopsychotic Vlporic acid
  • BRAINCODE Project: BWH MGH HMS

5:00 – 6:00 PM

AWARDS & RECEPTION

SPECIAL PHOTO-OP TO CELEBRATE YOU!
WE WILL TAKE A GROUP PHOTO DURING THE RECEPTION AND AWARDS CEREMONY TO CELEBRATE YOU, OUR INNOVATORS!
THE PHOTO WILL BE DISPLAYED AT THE BRIGHAM IN THE HALE BUILDING. WE HOPE YOU CAN JOIN US IN CELEBRATING YOUR ACHIEVEMENTS.

SOURCE

http://www.discoverbrigham.org/agenda/

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Obesity is a global concern that is associated with many chronic complications such as type 2 diabetes, insulin resistance (IR), cardiovascular diseases, and cancer. Growing evidence has implicated the digestive system, including its microbiota, gut-derived incretin hormones, and gut-associated lymphoid tissue in obesity and IR. During high fat diet (HFD) feeding and obesity, a significant shift occurs in the microbial populations within the gut, known as dysbiosis, which interacts with the intestinal immune system. Similar to other metabolic organs, including visceral adipose tissue (VAT) and liver, altered immune homeostasis has also been observed in the small and large intestines during obesity.

 

A link between the gut microbiota and the intestinal immune system is the immune-derived molecule immunoglobulin A (IgA). IgA is a B cell antibody primarily produced in dimeric form by plasma cells residing in the gut lamina propria (LP). Given the importance of IgA on intestinal–gut microbe immunoregulation, which is directly influenced by dietary changes, scientists hypothesized that IgA may be a key player in the pathogenesis of obesity and IR. Here, in this study it was demonstrate that IgA levels are reduced during obesity and the loss of IgA in mice worsens IR and increases intestinal permeability, microbiota encroachment, and downstream inflammation in metabolic tissues, including inside the VAT.

 

IgA deficiency alters the obese gut microbiota and its metabolic phenotype can be recapitulated into microbiota-depleted mice upon fecal matter transplantation. In addition, the researchers also demonstrated that commonly used therapies for diabetes such as metformin and bariatric surgery can alter cellular and stool IgA levels, respectively. These findings suggested a critical function for IgA in regulating metabolic disease and support the emerging role for intestinal immunity as an important modulator of systemic glucose metabolism.

 

Overall, the researchers demonstrated a critical role for IgA in regulating intestinal homeostasis, metabolic inflammation, and obesity-related IR. These findings identify intestinal IgA+ immune cells as mucosal mediators of whole-body glucose regulation in diet-induced metabolic disease. This research further emphasized the importance of the intestinal adaptive immune system and its interactions with the gut microbiota and innate immune system within the larger network of organs involved in the manifestation of metabolic disease.

 

Future investigation is required to determine the impact of IgA deficiency during obesity in humans and the role of metabolic disease in human populations with selective IgA deficiency, especially since human IgA deficiency is associated with an altered gut microbiota that cannot be fully compensated with IgM. However, the research identified IgA as a critical immunological molecule in the intestine that impacts systemic glucose homeostasis, and treatments targeting IgA-producing immune populations and SIgA may have therapeutic potential for metabolic disease.

 

References:

 

https://www.nature.com/articles/s41467-019-11370-y?elqTrackId=dc86e0c60f574542b033227afd0fdc8e

 

https://www.jci.org/articles/view/88879

 

https://www.nature.com/articles/nm.2353

 

https://diabetes.diabetesjournals.org/content/57/6/1470

 

https://www.sciencedirect.com/science/article/pii/S1550413115001047?via%3Dihub

 

https://www.sciencedirect.com/science/article/pii/S1550413115002326?via%3Dihub

 

https://www.sciencedirect.com/science/article/pii/S1931312814004636?via%3Dihub

 

https://www.nature.com/articles/nature15766

 

https://www.sciencedirect.com/science/article/pii/S1550413116000371?via%3Dihub

 

https://www.nature.com/articles/nm.2001

 

https://www.sciencedirect.com/science/article/abs/pii/S1550413118305047?via%3Dihub

 

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Engineered Bacteria used as Trojan Horse for Cancer Immunotherapy

Reporter: Irina Robu, PhD

Researchers are using synthetic biology— design and construction of new biological entities such as enzymes, genetic circuits, and cells or the redesign of existing biological systems—is changing medicine leading to innovative solution in molecular-based therapeutics. To address the issue of designing therapies that can induce a potent, anti-tumor immune response researchers at Columbia Engineering and Columbia Irving Medical Center engineered a strain of non-pathogenic bacteria that can colonize tumors in mice. The non-pathogenic bacteria act as Trojan Horse that can lead to complete tumor regression in a mouse model of lymphoma. Their results are currently published in Nature Medicine.

The scientists led by Nicholas Arpaia, used their expertise in synthetic biology and immunology to engineer a strain of bacteria able to grow and multiply in the necrotic core of tumors. The non-pathogenic E. coli are programmed to self-destruct when the bacteria numbers reach a critical threshold, allowing for actual release of therapeutics and averting them from causing havoc somewhere else in the body. Afterward, a small portion of bacteria survive lysis and repopulate the population which allows repeated rounds of drug delivery inside treated tumors.

In the present study, the scientists release a nanobody that targets CD47 protein, which defends cancer cells from being eaten by distinctive immune cells. The mutual effects of bacteria, induced local inflammation within the tumor and the blockage of the CD47 leads to better ingestion and activation of T-cells within the treated tumors. The team deduced that the treatment with their engineered bacteria not only cleared the treated tumors but also reduced the incidence of tumor metastasis.

Before moving to clinical trials, the team is performing proof-of-concept tests, safety and toxicology studies of their immunotherapeutic bacteria in a rand of advanced solid tumor settings in mouse models. They have currently collaborated with Gary Schwartz, deputy director of the Herbert Irving Comprehensive Cancer and have underway a company to translate their promising technology to patients.

SOURCE

Sreyan Chowdhury, Samuel Castro, Courtney Coker, Taylor E. Hinchliffe, Nicholas Arpaia, Tal Danino. Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nature Medicine, 2019

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