Volume 3.14 | Apr 14

Human Immunology News 3.14 April 14, 2015
Human Immunology News
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Enzyme Cuts Path for T-Cells to Fight Solid Tumors
Chimeric antigen rector-redirected T-cells specifically engineered to express the enzyme heparanase have an improved ability to infiltrate the extracellular matrix surrounding solid tumors – allowing the T-cells to infiltrate and shrink the tumors. [Press release from Baylor College of Medicine discussing online publication in Nature Medicine] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Inhibition of B-Raf/MEK/ERK Signaling Suppresses DR5 Expression and Impairs Response of Cancer Cells to DR5-Mediated Apoptosis and T Cell-Induced Killing
Investigators addressed whether B-Raf/MEK/ERK inhibition and the consequent suppression of death receptor 5 (DR5) expression impeded cancer cell response to DR5 activation-induced apoptosis and activated immune cell-induced killing. [Oncogene] Abstract

Extracellular Poly(ADP-Ribose) Is a Pro-Inflammatory Signal for Macrophages
Researchers found that poly(ADP-ribose) (PAR) activated cytokine release in human and mouse macrophages, a hallmark of innate immune activation, and determined structure-activity relationships. PAR was rapidly internalized by murine macrophages, while the monomer, ADP-ribose, was not. [Chem Biol]
Abstract | Graphical Abstract

T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self-Peptide Naturally Presented by HLA-B*18:01+ Cells
The authors describe a human self-peptide that is a homolog of a highly immunogenic EBV T cell epitope presented by HLA-B*18:01. A significant proportion of CD8+ T cells raised from some healthy individuals against this EBV epitope cross-reacted with the self-peptide. [J Immunol] Abstract

Regulatory T Cells-Derived IL-35 Promotes the Growth of Adult Acute Myeloid Leukemia Blasts
Scientists found that IL-35 was expressed highly in peripheral blood plasma of adult acute myeloid leukemia (AML) patients and significantly correlated with the clinical stages of malignancy. CD4+CD25+ regulatory T cells-derived from adult AML patients produced IL-35 in a stimulation-dependent manner. [Int J Cancer] Abstract

IL-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus Infected Macrophages
Investigators report that peripheral blood natural killer cells from human cytomegalovirus (HCMV) seropositive donors showed an enhanced activity towards HCMV infected autologous macrophages. [J Virol] Abstract

B7H6-Specific Chimeric Antigen Receptors Lead to Tumor Elimination and Host Anti-Tumor Immunity
B7H6, a ligand for the NK cell activating receptor NKp30, was targeted to create a chimeric antigen receptor (CAR) which targets multiple tumor types. B7H6-specific CAR T cells have robust cellular cytotoxicity and IFN‑γ secretion when co-cultured with B7H6+ tumor cells, and they exhibit little self-reactivity to immature dendritic cells or pro-inflammatory monocytes. [Gene Ther] Abstract

Engineering Monocyte-Derived Dendritic Cells to Secrete Interferon-α Enhances Their Ability to Promote Adaptive and Innate Anti-Tumor Immune Effector Functions
Scientists hypothesized that engineering easily generated human monocyte-derived mature dendritic cells to secrete interferon-α using mRNA electroporation enhances their ability to promote adaptive and innate anti-tumor immunity. [Cancer Immunol Immunother] Abstract

T Lymphocyte Density and Distribution in Human Colorectal Mucosa, and Inefficiency of Current Cell Isolation Protocols
The authors identified and quantified in human distal colorectal tissue absolute mucosal CD3+ lymphocytes, including CD4+ and CD8+ subsets, by direct visualization using immunohistochemistry, immunofluorescence, and an automated counting protocol. [PLoS One] Full Article

Functional Characterization of Human T Cell Hyporesponsiveness Induced by CTLA4-Ig
Scientists established a model to study the effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig showed that co-stimulation blockade during TCR activation did not affect NFAT signaling but resulted in decreased activation of NF-κB and AP-1 transcription factors followed by a profound decrease in proliferation and cytokine production. [PLoS One] Full Article

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Immune Checkpoint Targeting in Cancer Therapy: Toward Combination Strategies with Curative Potential
The authors discuss the evolution of research in two areas, genomics and immunology, and propose that intercrossing them and increasing funding to guide research of combination of agents represent a path forward for the development of curative therapies for the majority of cancer patients. [Cell] Full Article | Press Release

Neoantigens in Cancer Immunotherapy
Recent technological innovations have made it possible to dissect the immune response to patient-specific neoantigens that arise as a consequence of tumor-specific mutations, and emerging data suggest that recognition of such neoantigens is a major factor in the activity of clinical immunotherapies. [Science]
Abstract | Press Release

The Promise of γδ T Cells and the γδ T Cell Receptor for Cancer Immunotherapy
Ligand recognition by the γδ T cell receptor often requires accessory/co-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. The authors present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment. [Cell Mol Immunol] Abstract

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Ludwig Scientists to Present Advancements in Immunotherapy, Diagnostics, Cell Biology and Genomics
Ludwig Cancer Research previewed the full scope of discoveries to be presented by Ludwig scientists. [Press release from Ludwig Cancer Research discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting, San Diego] Press Release | Schedule

IOmet Pharma Demonstrates Superior In Vivo PK/PD Properties in Pre-Clinical IDO1, TDO and Dual IDO1/TDO Cancer Immunotherapy Programs
IOmet Pharma will present data demonstrating superior properties of its novel, pre-clinical IDO1, TDO and IDO1/TDO Dual Inhibitor programs. [Press release from IOmet Pharma discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting, San Diego] Press Release

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Memorial Sloan Kettering Opens First Pediatric CAR T Cell Clinical Trial
Researchers from Memorial Sloan Kettering Cancer Center are pioneering a new groundbreaking clinical trial for children and young adults with relapsed or treatment-resistant acute lymphocytic leukemia by using one of the most promising methods of cancer treatment, chimeric antigen receptor (CAR) T cells. [Memorial Sloan Kettering Cancer Center] Press Release

Roche Aims for 11 Late-Stage Trials in Cancer Immunotherapy Drug This Year
Roche aims to have an immunotherapy cancer drug in 11 late-stage trials by the end of the year, the Swiss drugmaker’s head of medical affairs for oncology, Nico Andre, said at a conference. [F. Hoffmann-La Roche Ltd. (Thomson Reuters)] Press Release
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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)
NEW ISSCR 2015 Annual Meeting
June 24-27, 2015
Stockholm, Sweden

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NEW Postdoctoral Fellow – Mucosal Immunology and Mycobiome (Cedars-Sinai Medical Center)

Postdoctoral Position – Immunology (Institut Curie)

Associate Scientist – Immunology and Stem Cell Biology (Nerdbio Inc.)

Postdoctoral Position – Immunology (University of Oxford)

Postdoctoral Position – Immunology (Moffitt Cancer Center & Research Institute)

Postdoctoral Position – Immunology (New York University School of Medicine)

Research Officer – Immunology (Glenmark Pharmaceuticals S.A.)

Manufacturing Manager – Cell Therapy (Opexa Therapeutics)

Senior Research Officer – Immunology (Glenmark Pharmaceuticals S.A.)

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