Volume 7.43 | Nov 13

Immune Regulation News 7.43 November 13, 2015
Immune Regulation News
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CD4+ T Cell Tolerance to Tissue-Restricted Self Antigens Is Mediated by Antigen-Specific Regulatory T Cells Rather Than Deletion
Researchers showed that endogenous CD4+ T cells with specificity for a set of tissue-restricted self antigens were not deleted at all. For pancreatic self antigen, this resulted in an absence of steady-state tolerance, while for the lung and intestine, tolerance was maintained by the enhanced presence of thymically-derived antigen-specific Foxp3+ regulatory T cells. [Immunity] Abstract | Graphical Abstract
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Selective Programming of CCR10+ Innate Lymphoid Cells in Skin-Draining Lymph Nodes for Cutaneous Homeostatic Regulation
Researchers found that under steady-state conditions, innate lymphoid cells in skin-draining lymph nodes were continuously activated to acquire regulatory properties and high expression of the chemokine receptor CCR10 for localization into the skin. [Nat Immunol] Abstract

CD20+ B Cell Depletion Therapy Suppresses Murine CD8+ T Cell-Mediated Immune Thrombocytopenia (ITP)
Scientists investigated the outcome of B cell depletion therapy on CD8+ T cell-mediated ITP using a murine model. CD61 knockout mice were immunized with CD61+ platelets and T cell-mediated ITP was initiated by transfer of their splenocytes into severe combined immunodeficient mice. [Blood] Abstract

An Extracatalytic Function of CD45 in B Cells Is Mediated by CD22
Researchers identified a noncatalytic role for CD45 in regulating tonic, but not antigen-mediated, B-cell antigen receptor signaling through modulation of the function of the inhibitory coreceptor CD22. [Proc Natl Acad Sci USA] Abstract | Full Article

Dendritic Cells Require NIK for CD40-Dependent Cross-Priming of CD8+ T Cells
Because NIK (NF-κB–inducing kinase)-deficient mice lack secondary lymphoid organs, scientists generated transgenic mice with targeted NIK deletion in CD11c+ cells. Although these mice exhibited normal lymphoid organs, they were defective in cross-priming naive CD8+ T cells following vaccination, even in the presence of anti-CD40 or polyinosinic:polycytidylic acid to induce dendritic cell maturation. [Proc Natl Acad Sci USA] Abstract | Full Article

Super Natural Killer Cells that Target Metastases in the Tumor Draining Lymph Nodes
The authors showed that liposomes decorated with apoptosis-inducing ligand TRAIL and an antibody against a mouse natural killer cell marker are carried to the tumor draining inguinal lymph nodes and prevent the lymphatic spread of a subcutaneous tumor in mice. [Biomaterials] Abstract | Press Release

MMP-19 Deficiency Causes Aggravation of Colitis Due to Defects in Innate Immune Cell Function
The authors explored the role of matrix metalloproteinase (MMP)-19 in IBD pathology. There was a striking delay in neutrophil infiltration into the colon of Mmp-19-deficient (Mmp-19−/−) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19−/− mice with wild-type bone marrow. [Mucosal Immunol] Abstract

IL-10-Producing CD4+ T Cells Negatively Regulate Fucosylation of Epithelial Cells in the Gut
Scientists showed that epithelial fucosylation in the ileum is negatively regulated by IL-10-producing CD4+ T cells. The number of fucosylated epithelial cells was increased in the ileum of mice lacking T cells, especially those expressing αβ T cell receptor, CD4, and IL-10. [Sci Rep] Full Article

Uric Acid Enhances the Antitumor Immunity of Dendritic Cell-Based Vaccine
Investigators applied uric acid (UA) as an adjuvant to a dendritic cells (DC)-based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. [Sci Rep] Full Article

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Regulatory T Cells in Cardiovascular Diseases
The authors provide an overview of the roles of regulatory T cells in the pathogenesis of a number of cardiovascular diseases, including atherosclerosis, hypertension, ischemic stroke, abdominal aortic aneurysm, Kawasaki disease, pulmonary arterial hypertension, myocardial infarction and remodeling, postischemic neovascularization, myocarditis and dilated cardiomyopathy, and heart failure. [Nat Rev Cardiol] Abstract

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OncoMed Presents Immuno-Oncology Data for Combined Blockade of DLL4, VEGF and PD1
OncoMed Pharmaceuticals Inc. presented new preclinical data for anti-DLL4 combined with anti-VEGF and anti-PD1. A series of preclinical experiments compared the impact of anti-DLL4/VEGF bispecific and a triple blockade of DLL4-VEGF-PD1 on anti-tumor immune responses. [Press release from OncoMed Pharmaceuticals Inc. discussing research presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC), National Harbor] Press Release

Kolltan Pharmaceuticals Presents Anti-KIT Antibody Preclinical Data
Kolltan Pharmaceuticals, Inc. announced results from preclinical studies using an anti-KIT monoclonal antibody to enhance T-cell checkpoint blockade in the treatment of cancer. [Press release from Kolltan Pharmaceuticals, Inc. discussing research presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC), National Harbor] Press Release

Research Underlying Galectin’s Development of GR-MD-02 in Cancer Presented
Galectin Therapeutics, Inc. announced that preclinical research from a study led by Stefanie Linch, Ph.D. was presented. The poster presentation is titled “Galectin-3 inhibition using novel inhibitor GR-MD-02 improves survival and immune function while reducing tumor vasculature.” [Press release from Galectin Therapeutics, Inc. discussing research presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC), National Harbor] Press Release | Poster

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Rutgers Cancer Institute of New Jersey Collaborates with Big Ten Cancer Research Consortium on Clinical Trial for Metastatic Kidney Cancer
In conjunction with the Big Ten Cancer Research Consortium, Rutgers Cancer Institute of New Jersey has opened a clinical trial for patients with kidney cancer that has spread to other parts of the body. The study, known as BTCRC-GU14-003, is examining a combination of pembrolizumab with bevacizumab for the treatment of patients with metastatic kidney cancer. [Rutgers Cancer Institute of New Jersey] Press Release

Targazyme and University of Minnesota Medical Center Initiate a Collaboration to Improve Regulatory T Cell Immunotherapy Outcomes for the Prevention and Treatment of Graft-versus-Host-Disease
Targazyme, Inc. announced that it has entered into a collaboration with the University of Minnesota Medical Center to advance the development of the company’s clinical product candidate, TZ101 for use with regulatory T cells. [Targazyme, Inc.] Press Release

Regen BioPharma Initiates NR2F6 T Cell Immunotherapy Preclinical Program with Dr. Santosh Kesari, Director of Neuro-Oncology at John Wayne Cancer Institute
Regen BioPharma Inc. announced the initiation of preclinical studies evaluating utilization of NR2F6 gene silencing as a means of stimulating the immune system in cancer patients with Dr. Santosh Kesari. The studies will examine whether initial observations in mouse immune cells that NR2F6 silencing can be translated into human immune cells. [Regen BioPharma Inc. (PR Newswire Association LLC)] Press Release

ImmunoCellular Therapeutics Enters into Sponsored Research Agreement with University of Texas MD Anderson Cancer Center to Advance Stem-to-T-Cell Program
ImmunoCellular Therapeutics, Ltd. announced it has entered into a sponsored research agreement with Dr. Cassian Yee at the University of Texas MD Anderson Cancer Center. The ultimate goal of this work is to enable a clinical program based on hematopoietic stem cells that are isolated from the patient, engineered in the lab and then returned to the patient to create a population of antigen-specific killer T cells that target and kill the tumor. [ImmunoCellular Therapeutics, Ltd.] Press Release

The University of Kansas Cancer Center Is the First in the World to Enroll Adults in Immunotherapy Trial
A novel immunotherapy clinical trial underway now at The University of Kansas Cancer Center. T-cells taken from the patient are modified and multiplied and then given back to the patient through an infusion. [The University of Kansas Cancer Center] Press Release

Immune Design Announces Start of Randomized Phase II Cancer Immunotherapy Combination Trial in Patients with Soft Tissue Sarcoma
Immune Design announced the start of a randomized Phase II trial of CMB305, the company’s “prime boost” cancer immunotherapy product candidate, combined with Genentech’s investigational cancer immunotherapy, atezolizumab in patients with soft tissue sarcoma. [Immune Design] Press Release
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NEW Staff Scientist – Immunology (Benaroya Research Institute at Virginia Mason)

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

Scientist – Preclinical Immunology (Kanyos Bio)

Senior Research Fellow – Cancer Biology/Immunology (Plymouth University)

Postdoctoral Fellow – Regulatory Functions of Immune-Checkpoint Proteins (Medical College of Wisconsin)

Faculty Positions – Tumor Immunology (NYU Langone Medical Center)

Postdoctoral Fellow – Metastatic Breast Cancer (Purdue University Center for Cancer Research)

Postdoctoral Fellow – Cancer Biology (The University of Texas MD Anderson Cancer Center)

Professor – Immunology (La Jolla Institute for Allergy & Immunology)

Canadian Research Chair Tier 1 – Systems Immunology (University of Manitoba)

Scientist Position – Role of Inflammation and the Immune System in the Context of Tissue Regeneration (KU Leuven)

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