Volume 3.40 | Oct 13

Human Immunology News 3.40 October 13, 2015
Human Immunology News
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
Turning T Cell Immunology on Its Head
Until now, the assumption has been that the receptors on the T cells (TCRs) must bind to the major histocompatibility complex (MHC) in a specific orientation in order to trigger a signal to the immune system. Researchers demonstrated for the first time that TCRs can bind with a completely reversed orientation — compared to all previously studied receptors. [Press release from the Centre for Advanced Molecular Imaging discussing online prepublication in Nature Immunology] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells
Using an in vivo “stress test” to challenge CD19-targeted T cells, scientists studied the functionality and persistence imparted by seven different chimeric antigen receptor (CAR) structures providing CD28 and/or 4-1BB costimulation. [Cancer Cell] Full Article | Graphical Abstract

TCR Sequencing Facilitates Diagnosis and Identifies Mature T Cells as the Cell of Origin in CTCL
Analysis of cutaneous T cell lymphoma (CTCL) T cell receptor γ genes demonstrated that CTCL is a malignancy derived from mature T cells. There was a maximal T cell density in skin in benign inflammatory diseases that was exceeded in CTCL, suggesting that a niche of finite size may exist for benign T cells in skin. [Sci Transl Med] Abstract | Press Release

Sialylation of IgG Fc Domain Impairs Complement-Dependent Cytotoxicity
The authors report that IgG fragment crystallizable (Fc) sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity. Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating Fcγ receptors. [J Clin Invest] Full Article | Press Release

Tamoxifen Augments the Innate Immune Function of Neutrophils through Modulation of Intracellular Ceramide
Researchers found that tamoxifen stimulation enhances several pro-inflammatory pathways in human neutrophils, including chemotaxis, phagocytosis and neutrophil extracellular trap formation. [Nat Commun] Abstract | Press Release

Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human
Scientists report the presence of a cell population in the bone marrow of the cytokine-treated humanized mice that express both natural killer cell marker CD56 and myeloid markers such as CD36 and CD33. The CD56+CD33+CD36+ cells are also found in human cord blood, fetal and adult bone marrow. [Sci Rep] Full Article

Direct Tumor Recognition by a Human CD4+ T-Cell Subset Potently Mediates Tumor Growth Inhibition and Orchestrates Anti-Tumor Immune Responses
The authors characterized anti-tumor effects of a unique human CD4+ helper T-cell subset that directly recognizes the cytoplasmic tumor antigen, NY-ESO-1, presented by MHC class II on cancer cells. Upon direct recognition of cancer cells, tumor-recognizing CD4+ T cells potently induced IFN-γ-dependent growth arrest in cancer cells. [Sci Rep] Full Article | Press Release

Langerin-Mediated Internalization of a Modified Peptide Routes Antigens to Early Endosomes and Enhances Cross-Presentation by Human Langerhans Cells
Investigators showed that primary human Langerhans cells (LCs) were able to cross-present a synthetic long peptide to CD8+ T cells. The potency of LCs to enhance CD8+ T-cell responses could be further increased through activation of LCs with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid. [Cell Mol Immunol] Abstract

Lenalidomide Enhances the Function of Chimeric Antigen Receptor T Cells against the Epidermal Growth Factor Receptor Variant III by Enhancing Immune Synapses
Scientists constructed a lentiviral vector transducing the chimeric antigen receptor (CAR) that consisted of 3C10-scFv, CD3ζ, CD28 and 4-1BB (3C10-CAR). The 3C10-CAR-transduced peripheral blood mononuclear cells and CD3+ T cells specifically lysed the glioma cells that express epidermal growth factor receptor variant III. [Cancer Gene Ther] Abstract

Lymphocyte Phosphatase-Associated Phosphoprotein Proteoforms Analyzed Using Monoclonal Antibodies
Researchers determined the pattern of lymphocyte phosphatase-associated phosphoprotein (LPAP) expression in various cell types and characterized its proteoforms using new monoclonal antibodies generated against the intracellular portion of the protein. They showed that LPAP is a pan-lymphocyte marker, and its expression in cells correlates with the expression of CD45. [Clin Transl Immunol] Full Article

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REVIEWS
γδ T Cells in Cancer
Investigators integrate the current knowledge from both human and mouse studies to highlight the potential of γδ T cell modulation to improve cancer immunotherapy. [Nat Rev Immunol] Abstract

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SCIENCE NEWS
OncBioMune Presents Data on Novel Cancer Vaccine ProscaVax
OncBioMune Pharmaceuticals, Inc. announced that Dr. Jonathan Head presented interim data on the company’s Phase I clinical trial of the novel vaccine ProscaVax for prostate cancer. [Press release from OncBioMune Pharmaceuticals, Inc. (Marketwired L.P.) discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release | Presentation

SELLAS Life Sciences Reports Promising Top-Line Phase II Data for WT1 Vaccine in Mesothelioma and Acute Myeloid Leukemia Patients
SELLAS Life Sciences Group announced top-line data from the company’s Phase II clinical study of its WT1 cancer vaccine in patients with malignant pleural mesothelioma. [Press release from SELLAS Life Sciences Group (PR Newswire Association, LLC) discussing research to be presented at the 8th International WT1 Conference, Kyoto] Press Release

Advaxis’s Cancer Immunotherapies to Be Featured in Three Poster Presentations
Advaxis, Inc. announced that three abstracts featuring Advaxis’s Lm Technology™ cancer immunotherapies have been selected for poster presentation. [Press release from Advaxis, Inc. discussing research to be presented at the Society for Immunotherapy of Cancer’s (SITC) 30th Anniversary Annual Meeting, National Harbor] Press Release

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INDUSTRY NEWS
Human Vaccines Project Partners with MedImmune to Help Accelerate Research and Development in Infectious Disease and Oncology
MedImmune is the newest member of the Human Vaccines Project, which will help to accelerate the research and development of vaccines and immunotherapies for infectious disease and cancer. [MedImmune, LLC] Press Release

Cancer Research UK Launches £100 Million Grand Challenges to Tackle the Most Important Questions in Cancer
Cancer Research UK has launched Grand Challenges – the biggest and most ambitious cancer grants in the world – which aim to overcome the greatest barriers standing in the way of beating cancer. The £100 million investment will revolutionize how we diagnose, prevent and treat cancer by uniting teams of the best scientists around the world to come up with answers to crucial questions about how to save more lives from cancer. [Cancer Research UK] Press Release

NYBC Laboratories Receive almost $4 Million in NIH Grants
NYBC’s Laboratory of Complement Biology at its Lindsley F. Kimball Research Institute has received a significant federal grant to identify the immune cells that block medications commonly used to treat patients with immune thrombocytopenia – an autoimmune bleeding disease in which patients attack and destroy their own platelets, the blood component primarily responsible for controlling bleeding. [New York Blood Center (NYBC)] 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 Keystone Symposium: Cytokine JAK-STAT Signaling in Immunity and Disease
January 10-14, 2016
Steamboat Springs, United States

Visit our events page to see a complete list of events in the Human Immunology community.
 
JOB OPPORTUNITIES
NEW Project Manager – Manufacturing (Qu Biologics)

NEW Postdoctoral Research Fellow/Research Scientist – Biotechnology (Qu Biologics)

Postdoctoral Position – Tumor Immunology (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Cancer Immunology/Immunotherapy (Universität Basel)

Postdoctoral Positions – Immunology (Shanghai Institute of Immunology)

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

Principal Investigator – The Role of Inflammation and the Immune Response in Regenerative Medicine (KU Leuven)

Scientist – Human T Cell Immunology (Innate Pharma S.A.)

Postdoctoral Research Associate – Systems Immunology/Bioinformatics (Benaroya Research Institute at Virginia Mason (BRI))

Tenure Track or Early Career/Tenured Investigator – Immunology (National Institutes of Health – National Heart, Lung, and Blood Institute)

Postdoctoral Position – Neuroimmunology (Brain and Spine Institute (ICM))


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