Volume 8.10 | Mar 18

Immune Regulation News 8.10 March 18, 2016
Immune Regulation News
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
Scientists Modulate Cholesterol Metabolism to Potentiate T-Cell Antitumor Immunity
Researchers found that inhibiting cholesterol esterification can potentiate the antitumor activity of CD8+ T cells. This new way of improving T-cell function might be used as a complement to current cancer immunotherapies, such as immune checkpoint blockade. [Press release from the Chinese Academy of Sciences discussing online prepublication in Nature] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
The Amino Acid Sensor GCN2 Controls Gut Inflammation by Inhibiting Inflammasome Activation
Genetic deletion of Gcn2 in CD11c+ antigen presenting cells or intestinal epithelial cells resulted in enhanced intestinal inflammation and T helper 17 cell responses, owing to enhanced inflammasome activation and interleukin-1β production. [Nature] Abstract | Press Release

The Maternal Microbiota Drives Early Postnatal Innate Immune Development
By transiently colonizing pregnant female mice, scientists showed that the maternal microbiota shapes the immune system of the offspring. Gestational colonization increased intestinal group 3 innate lymphoid cells and F4/80+CD11c+ mononuclear cells in the pups. [Science] Abstract | Press Release

C9orf72 Is Required for Proper Macrophage and Microglial Function in Mice
C9orf72 expression was highest in myeloid cells, and the loss of C9orf72 led to lysosomal accumulation and altered immune responses in macrophages and microglia, with age-related neuroinflammation similar to C9orf72 amyotrophic lateral sclerosis (ALS) but not sporadic ALS human patient tissue. [Science]
Abstract | Press Release

Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade
Researchers demonstrated that sufficient T cell infiltration in tumor tissues is a prerequisite for response to PD-L1 blockade. Targeting tumors with tumor necrosis factor superfamily member LIGHT activates lymphotoxin β-receptor signaling, leading to the production of chemokines that recruit massive numbers of T cells. [Cancer Cell] Abstract | Graphical Abstract | Press Release

Type 1 Diabetes Vaccine Candidates Promote Human Foxp3+ Treg Induction in Humanized Mice
Researchers identified HLA-DQ8-restricted insulin-specific CD4+ T cells and demonstrated efficient human insulin-specific Foxp3+ regulatory T cell (Treg)-induction upon subimmunogenic vaccination with strong agonistic insulin mimetopes in vivo. [Nat Commun] Full Article | Press Release

Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells
Scientists showed that saturated fatty acids (SFAs), when in excess, induce a unique transcriptional signature in both mouse and human macrophages that is enriched by a subset of ER stress markers, particularly IRE1α and many adaptive downstream target genes. SFAs also activate the NLRP3 inflammasome in macrophages, resulting in IL-1β secretion. [Cell Rep] Full Article | Graphical Abstract | Press Release

The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells
Investigators showed that intracellular interleukin (IL)-12 localizes in late endocytic vesicles marked by the SNARE VAMP7. Dendritic cells (DCs) from VAMP7-deficient mice are partially impaired in the multidirectional release of IL-12. Consistently, acquisition of effector functions is reduced in T cells stimulated by VAMP7-null DCs. [Cell Rep] Full Article | Graphical Abstract

Antigen-Encoding Bone Marrow Terminates Islet-Directed Memory CD8+ T-Cell Responses to Alleviate Islet Transplant Rejection
Researchers showed that transfer of bone marrow encoding cognate antigen directed to dendritic cells, under mild, immune-preserving conditions inactivates established memory CD8+ T-cell populations and generates a long-lived, antigen-specific tolerogenic environment. [Diabetes] Abstract

IL-27 Suppresses Type 2 Immune Responses In Vivo via Direct Effects on Group 2 Innate Lymphoid Cells
The authors provide compelling evidence that IL-27-signaling directly inhibits group 2 innate lymphoid cells responses and reveal a novel mechanism for negative regulation of the innate arm of type-2 immunity. [Mucosal Immunol] Abstract

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REVIEWS
Targeting Dendritic Cells: A Promising Strategy to Improve Vaccine Effectiveness
The authors review the complexity of the dendritic cell (DC) subsets and the antigen presentation pathways that need to be considered in the settings of DC targeting. They also summarize current knowledge about antigen delivery to DCs via DEC-205, Clec9A and Clec12A, receptor targets that strongly enhance cellular and humoral immune responses. [Clin Transl Immunol] Full Article

Visit our reviews page to see a complete list of reviews in the immune regulation research field.
 
SCIENCE NEWS
Cellular ‘Backpacks’ Could Treat Disease While Minimizing Side Effects
To send drugs to specific disease locations and avoid unwanted symptoms, researchers developed cellular “backpacks” that are designed to carry a therapeutic cargo only to inflamed disease sites. The resulting pack has different functional regions. One is Velcro-like, attaching via antibody-antigen binding to immune cells, such as monocytes and macrophages. [Press release from the American Chemical Society (ACS) discussing research presented at the 251st National Meeting & Exposition of the ACS, San Diego] Press Release

Kite Pharma Announces Clinical and Manufacturing Updates on KTE-C19 and MAGE-A3 Product Candidates
Kite Pharma, Inc. announced two oral presentations and two poster presentations to be delivered. The oral presentations will address KTE-C19, Kite’s lead chimeric antigen receptor product candidate, and, separately, an engineered T cell receptor product candidate targeting the cancer testis antigen MAGE-A3. [Press release from Kite Pharma, Inc. discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2016, New Orleans] Press Release

Celsion Announces Presentation of Preclinical Data for GEN-1 IL-12 Immunotherapy in Combination with Avastin® and Doxil®
Celsion Corporation announced that its preclinical data for GEN-1 in combination with Avastin® and Doxil® for the treatment of ovarian cancer will be presented. [Press release from Celsion Corporation discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2016, New Orleans] Press Release

MacroGenics Announces Five Posters at AACR Annual Meeting 2016
MacroGenics, Inc. announced that it will present five posters. Four of the five posters refer to programs that are based on MacroGenics’ Dual-Affinity Re-Targeting (DART®) bispecific technology. [Press release from MacroGenics, Inc. discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2016, New Orleans] Press Release

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INDUSTRY NEWS
Kite Pharma Announces Clinical Collaboration to Evaluate Two Novel Immunotherapies for Patients with Non-Hodgkin Lymphoma
Kite Pharma, Inc. announced that it has entered into a clinical trial collaboration with Genentech, a member of the Roche Group, to evaluate the safety and efficacy of KTE-C19, in combination with atezolizumab, in patients with refractory, aggressive non-Hodgkin lymphoma. [Kite Pharma, Inc.] Press Release

Profectus and Vyriad Form Global Collaboration to Develop Oncolytic Recombinant VSV (RVSV) Vaccines for Cancer Immunotherapy
The two companies will combine and leverage their respective recombinant vesicular stomatitis virus (rVSV)-derived oncolytic and vaccine platform technologies to develop novel cancer drugs that selectively destroy tumor cells while simultaneously boosting patients’ immune systems to continue killing any residual cancer cells that may survive the initial virus attack. [Vyriad] Press Release
 
POLICY NEWS
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
 
EVENTS
NEW The Power of Our Cells to Revolutionize Medicine
March 24, 2016
Ottawa, Canada

NEW Summit for Cancer Immunotherapy
June 26-29, 2016
Halifax, Canada

NEW North American Adoptive T-Cell Therapy Congress
June 29-30, 2016
Boston, United States

Visit our events page to see a complete list of events in the immune regulation community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Fellow – Immunology (Boston Children’s Hospital)

NEW Postdoctoral Researchers – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Position or Research Scientist – Mucosal Immunology (Qu Biologics)

Immunologist (GlaxoSmithKline plc)

Postdoctoral Fellow – Clinical Immunology (Benaroya Research Institute at Virginia Mason)

Postdoctoral Fellow – Autoimmune, Inflammatory and Demyelinating Diseases (Queen’s University Belfast)

Postdoctoral Positions – Innate Immunity and Autoimmunity (UT Southwestern Medical Center)

Faculty Positions – Immunology (University of Texas Health Science Center)

Assistant or Associate Professor – Immunity and Tolerance (Cincinnati Children’s Hospital Medical Center)


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