Human Immunology News Volume 4.14 | Apr 12 2016

Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
Analyzing the invasive margin of human colorectal cancer liver metastases, investigators identified a mechanism of immune cell exploitation by tumor cells. While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5. [Cancer Cell] Abstract | Graphical Abstract

Targeting Non-Proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma
Researchers showed that the CARD11-MALT1-BCL10 complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of B cell receptor-dependent NF-κB activity in the activated B cell-like subtype of diffuse large B cell lymphoma. [Cancer Cell] Abstract

Zinc-Induced Polymerization of Killer-Cell Ig-Like Receptor into Filaments Promotes Its Inhibitory Function at Cytotoxic Immunological Synapses
The inhibitory function of killer cell immunoglobulin-like receptors (KIR) that bind HLA-C and block activation of human natural killer cells is dependent on zinc. The authors report that zinc induced the assembly of soluble KIR into filamentous polymers, as detected by electron microscopy, which depolymerized after zinc chelation. [Mol Cell] Abstract | Graphical Abstract

OX40⁺ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T Cell Responses and Associate with Metastatic Potential
To investigate reasons for failure of T cells to mount a protective response in cutaneous squamous cell carcinoma, scientists focused on regulatory T cells as this suppressive population is well represented among the infiltrating lymphocytes. [Clin Cancer Res] Abstract | Full Article

CD4⁺ and CD8⁺ TCRβ Repertoires Possess Different Potentials to Generate Extraordinarily High-Avidity T Cells
Researchers showed that the transduction of SIG35α, the public chain-centric HLA-A*02:01(A2)/MART127–35 TCRα hemichain, conferred A2/MART127–35 reactivity to a substantial subset of both CD8⁺ and CD4⁺ T cells regardless of their HLA–A2 positivity. [Sci Rep] Full Article

Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF Levels in Response to the T Cell Independent Immunogen Pneumovax^®23
Researchers analyzed the effect of a T cell independent antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide-based vaccine Pneumovax^®23, and subsequent characterization of B cell subpopulations. [PLoS One] Full Article

Differential Effects of the Two Amino Acid Sensing Systems, the GCN2 Kinase and the mTOR Complex 1, on Primary Human Alloreactive CD4⁺ T-Cells
The effects of general control nonderepressible 2 (GCN2) kinase activation or mammalian target of rapamycin (mTOR) inhibition on human alloreactive CD4⁺ T-cells were evaluated. The mixed lymphocyte reaction, as a model of alloreactivity, the GCN2 kinase activator, tryptophan, and the mTOR complex 1 inhibitor, rapamycin, were used. [Int J Mol Med] Abstract

A Multi-Laboratory Comparison of Blood Dendritic Cell Populations
The authors validated a backbone of monoclonal antibodies (mAbs) to delineate monocyte and dendritic cell (DC) populations from peripheral blood. The mAb backbone allowed identification of monocyte and DC subsets using fluorochromes that were compatible with most ‘off the shelf’ or routine flow cytometers. [Clin Transl Immunol] Full Article

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Synthetic Glycolipid Activators of Natural Killer T Cells as Immunotherapeutic Agents
Investigators discuss the design of synthetic glycolipid activators for invariant natural killer T (iNKT) cells, their impact on adaptive immune responses and their use to modulate iNKT cell responses to improve immunity against infections and cancer. [Clin Transl Immunol] Full Article

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Immunovaccine to Present New Pre-Clinical Data
Immunovaccine Inc. announced that new pre-clinical data on DPX™-based cancer vaccines will be presented. [Press release from Immunovaccine Inc. discussing research to be presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release | Abstract

Premier Biomedical, Inc. Cancer Immunotherapy Research Highlights to Be Presented
Premier Biomedical, Inc. announced additional details regarding the presentation of the results of their cancer immunotherapy research, along with additional research results by their UTEP scientist partners. [Press release from Premier Biomedical, Inc. discussing research to be presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release | Abstract

Aduro Biotech Chief Scientific Officer to Highlight the Potential of STING Activation in Cancer Immunotherapy
Thomas W. Dubensky, Jr., Ph.D. will highlight Aduro’s landmark first-in-human immunotherapeutic approach in cancer to target the stimulator of interferon genes (STING) pathway. [Press release from Aduro Biotech, Inc. discussing research to be presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release | Abstract

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UAB Awarded $19.5 Million Grant for New Xenotransplantation Program
The University of Alabama at Birmingham Comprehensive Transplant Institute has been awarded a five-year, $19.5 million grant from biotechnology magnate United Therapeutics Corporation to launch a pioneering UAB Xenotransplantation Program that both groups hope will lead to genetically modified kidney transplants from pig models to humans by 2021. [University of Alabama at Birmingham] Press Release

Type 1 Diabetes Cell Therapy Trial Enrolls First Patient at Sanford
A clinical trial studying the body’s ability to type fight 1 diabetes using cell therapy has used the method on its first participant. “The Sanford Project: T-Rex Study” is a collaborative study between Sanford Health and Caladrius Biosciences, Inc., for adolescents with newly onset type 1 diabetes. [Sanford Health] Press Release

BriaCell Files a Patent Application to Protect Additional Cancer Vaccines with Genetic Features Thought to Promote Strong Anti-Tumor Activity
BriaCell Therapeutics Corp. announced that it has filed a provisional patent application with the U.S. Patent and Trademark Office outlining certain features thought to improve clinical efficacy of whole-cell cancer vaccines. [BriaCell Therapeutics Corp.] Press Release

FDA Grants Priority Review for Genentech’s Cancer Immunotherapy Atezolizumab in Specific Type of Lung Cancer
Genentech announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application and granted Priority Review for atezolizumab for the treatment of people with locally advanced or metastatic non-small cell lung cancer whose disease expresses the protein PD-L1 (programmed death ligand-1) and who have progressed on or after platinum-containing chemotherapy. [Genentech, Inc.] Press Release

Therapeutic Solutions International’s Subsidiary MolecuVax, Inc. to Initiate Cancer Immunotherapy Clinical Trial Aimed at Eradicating Cancer Stem Cells Using MVAX-001
Therapeutic Solutions International, Inc. announced the signing of an agreement between its subsidiary, MolecuVax, Inc., and the Pan Am Cancer Treatment Center covering production and clinical implementation of a novel cancer immunotherapy based around MVAX’s proprietary Brother of the Regulator of Imprinted Sites peptide/exosome technology. [Therapeutic Solutions International, Inc.] Press Release

FDA Approves Celltrion’s INFLECTRA™ (Biosimilar Infliximab) for All Indications
Celltrion announced that the U.S. Food and Drug Administration (FDA) has approved INFLECTRA™ for all indications of the reference product, Janssen Biotech Inc.’s Remicade^® (infliximab). [Celltrion, Inc.] Press Release

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)

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NEW Engineering Project Lead (Cytonome)

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

Postdoctoral Position – Human Immune System-Microbiota Crosstalk (Karolinska Institutet)

Postdoctoral Fellow – Immunology (University of Wisconsin – Madison)

Masters Student – Immunology (Trinity College Dublin)

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

Postdoctoral Fellow – Immunology (Ragon Institute of MGH, MIT and Harvard)

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

Tenure-Track Position – Immunology (Massachusetts General Hospital)

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

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