Volume 6.38 | Oct 10

Immune Regulation News 6.38 October 10, 2014
Immune Regulation News
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De Novo Fatty Acid Synthesis Controls the Fate between Regulatory T and T Helper 17 Cells
Researchers report that inhibition of acetyl-CoA carboxylase 1 (ACC1) restrains the formation of human and mouse T helper (TH)17 cells and promotes the development of anti-inflammatory Foxp3+ regulatory T (Treg) cells. They show that TH17 cells, but not Treg cells, depend on ACC1-mediated de novo fatty acid synthesis and the underlying glycolytic-lipogenic metabolic pathway for their development. [Nat Med] Abstract
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The Ion Channel TRPV1 Regulates the Activation and Proinflammatory Properties of CD4+ T Cells
Scientists found that TRPV1 was functionally expressed in CD4+ T cells, where it acted as a non-store-operated Ca2+ channel and contributed to T cell antigen receptor (TCR)-induced Ca2+ influx, TCR signaling and T cell activation. In models of T cell-mediated colitis, TRPV1 promoted colitogenic T cell responses and intestinal inflammation. [Nat Immunol] Abstract | Press Release

Rhinovirus-Induced IL-25 in Asthma Exacerbation Drives Type 2 Immunity and Allergic Pulmonary Inflammation
Investigators examined whether rhinoviruses (RV)-induced interleukin (IL)-25 could contribute to asthma exacerbations. Blockade of the IL-25 receptor reduced many RV-induced exacerbation-specific responses including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells. [Sci Transl Med] Abstract | Press Release

NK1.1+ CD8+ T Cells Escape TGF-β Control and Contribute to Early Microbial Pathogen Response
Investigators report that an effector CD8+ T-cell population that expresses the marker ​NK1.1 undergoes delayed contraction and sustains early anti-microbial protection. ​NK1.1+ CD8+ T cells are derived from CD8+ T cells during priming, and their differentiation is inhibited by transforming growth factor-β signaling. [Nat Commun] Abstract

NAD+ Protects against EAE by Regulating ​CD4+ T-Cell Differentiation
Investigators show that ​nicotinamide adenine dinucleotide (​NAD+) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, by inducing immune homeostasis through ​
CD4+​IFNγ+​IL-10+ T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. [Nat Commun]
Full Article | Press Release

Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade
Fractionated radiotherapy delivered in combination with αPD-1 or αPD-L1 mAbs generated efficacious CD8+ T-cell responses that improved local tumor control, long-term survival, and protection against tumor rechallenge. These favorable outcomes were associated with induction of a tumor antigen-specific memory immune response. [Cancer Res] Abstract | Press Release

NF-κB Functions in Tumor Initiation by Suppressing the Surveillance of Both Innate and Adaptive Immune Cells
Scientists demonstrate that, following immortalization, p65 switches to an oncogene by counteracting the surveillance properties of immune cells. NF-κB exerts this effect by protecting transformed cells against macrophage-derived proapoptotic factors, tumor necrosis factor, and nitric oxide. [Cell Rep]
Full Article | Graphical Abstract | Press Release

The Bullseye Synapse Formed between CD4+ T-Cells and Staphylococcal Enterotoxin B-Pulsed Dendritic Cells Is a Suppressive Synapse in T-Cell Response
Researchers found that the bullseye immunological synapse (IS), one type of IS at the interface of CD4+ T cells and staphylococcal enterotoxin B-pulsed dendritic cells, suppressed CD4+ T-cell activation, whereas multifocal IS, another synapse type, stimulated CD4+ T-cell activation. [Immunol Cell Biol] Abstract

Overexpression of Jagged-1 Combined with Blockade of CD40 Pathway Prolongs Allograft Survival
Scientists investigated whether blockade of the CD40 pathway could enhance the immune tolerance induced by dendritic cell 2.4 cells modified to express Jagged-1 in heart transplantation. The therapy specifically inhibited the immune response, induced alloantigen-specific T-cell hyporesponsiveness, upregulated transforming growth factor-β synthesis and increased the population of regulatory T cells driven by Jagged-1-Notch activation. [Immunol Cell Biol] Abstract

Intramuscular Delivery of Heterodimeric IL-15 DNA in Macaques Produces Systemic Levels of Bioactive Cytokine Inducing Proliferation of NK and T Cells
Investigators have generated DNA vectors expressing the heterodimeric interleukin (IL)-15 by optimizing mRNA expression and protein trafficking. Administration of DNAs expressing heterodimeric IL-15 resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. [Gene Ther] Full Article

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Autophagy in T-Cell Development, Activation and Differentiation
First described as a survival mechanism during nutrient starvation conditions, recent reports have demonstrated that autophagy supports metabolic functions of T cells at various stages of maturation and effector function. [Immunol Cell Biol] Abstract

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PS-Targeting Antibodies Enhance the Anti-Tumor Activity of Immune Checkpoint Inhibitors by Decreasing Levels of Myeloid Derived Suppressor Cells (MDSC) in the Tumor Microenvironment
Peregrine Pharmaceuticals, Inc. announced the presentation of preclinical data related to the company’s immuno-oncology development program and its lead drug candidate bavituximab, a phosphatidylserine (PS)-targeting antibody. [Press release from Peregrine Pharmaceuticals, Inc. discussing research presented at the 22nd Annual International Cancer Immunotherapy Symposium, New York] Press Release

TxCell to Present Latest Developments of Its Personalized Cell-Based Immunotherapy Platform, ASTrIA
TxCell SA provided an overview of the development and progress of ASTrIA, TxCell’s innovative proprietary technological platform. [Press release from TxCell SA discussing research presented at the 13th Annual BIO Investor Forum, San Francisco] Press Release

Genocea Presents Complete Phase I/IIa Data for HSV-2 Immunotherapy at IDWeek
Genocea Biosciences, Inc. announced the presentation of final data from the Phase I/IIa study of GEN-003, the company’s immunotherapy candidate for treatment of genital herpes. [Press release from Genocea Biosciences, Inc. discussing research to be presented at IDWeek™, Philadelphia] Press Release

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$1 Million National Cancer Institute Grant Will Advance UCLA Research on Vault Nanomedicine Treatment for Lung Cancer
A $1 million grant from the National Cancer Institute’s Small Business Innovation Research program will enable UCLA scientists and industry partners to take an innovative lung cancer treatment through the final steps toward its first clinical trial. The treatment combines an immunotherapy agent called CCL21 with a drug delivery nanotechnology using biological particles called vaults. [UCLA] Press Release

Amgen’s BiTE® Immunotherapy Blinatumomab Receives FDA Priority Review Designation in Acute Lymphoblastic Leukemia
Amgen announced that the U.S. Food and Drug Administration (FDA) has accepted for review the biologics license application for the investigational bispecific T cell engager (BiTE®) antibody construct, blinatumomab. [Amgen, Inc.] Press Release

Medigene Receives Patent for TCR-Modified T Cell Immunotherapy in Australia
Medigene AG announced that the Australian Patent Office has issued patent No. 2009317161 titled “High affinity T cell receptor and use thereof,” relating to T-cell receptors against the tumor associated antigen tyrosinase. [Medigene AG] Press Release
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Therapeutic Goods Administration (Australia)
NEW The Fourth International Conference on Regulatory T Cells and TH Subsets and Clinical Application in Human Diseases
November 1-4, 2014
Shanghai, China

NEW 43rd Autumn Immunology Conference (AIC) 2014
November 21-24, 2014
Chicago, United States

NEW Cell Symposia: The Multifaceted Roles of Type 2 Immunity
December 10-12, 2014
Bruges, Belgium

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NEW Postdoctoral Fellow – Immunology (Beth Israel Deaconess Medical Center – Harvard Medical School)

PhD Position – Immunoregulation (Jena University Hospital)

Postdoctoral Position – Immunometabolism (INSERM)

PhD Student – Calcium and Redox Signaling in Immune and Skin Cells (University of Saarland)

Postdoctoral Fellowship – Development of Autoimmunity and Cancer (Mount Sinai Medical Center)

Postdoctoral Researcher – Immune Response to Cancer (INSERM)

Postdoctoral Position – Immunology (Western New England University)

Faculty Positions – Cancer Immunotherapy and Tumor Microenvironment (NYU Langone Medical Center)

Postdoctoral Position – Transplantation Aspects of Hepatocytes Derived from Human Pluripotent Stem Cells (INSERM UMR 1064)

PhD Studentship – Cancer Immunology (Cardiff University)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

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