Volume 3.38 | Sep 29

Human Immunology News 3.38 September 29, 2015
Human Immunology News
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Vaccination on the Horizon for Severe Viral Infection of the Brain
Researchers reveal possible new treatment methods for a rare, usually fatal brain disease. Thanks to their discovery that specific antibodies play a key role in combating the viral infection, a vaccine against the disease “progressive multifocal leukoencephalopathy” could now be developed. [Press release from University of Zurich discussing online publication in Science Translational Medicine] Press Release | Abstract 1 | Abstract 2
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PUBLICATIONS (Ranked by impact factor of the journal)
Remote Control of Therapeutic T Cells through a Small Molecule–Gated Chimeric Receptor
Investigators present the design of “ON-switch” chimeric antigen receptors that enable small molecule-control over T cell therapeutic functions, while still retaining antigen specificity. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. [Science] Abstract | Press Release | Video

Glycolysis Controls the Induction of Human Regulatory T Cells by Modulating the Expression of FOXP3 Exon 2 Splicing Variants
Researchers found that the induction and suppressive function of induced human regulatory T cells tightly depended on glycolysis, which controlled Foxp3 splicing variants containing exon 2 through the glycolytic enzyme enolase-1. [Nat Immunol] Abstract

Tumor PD-L1 Expression, Immune Cell Correlates and PD-1+ Lymphocytes in Sentinel Lymph Node Melanoma Metastases
Scientists aimed to characterize, in sentinel lymph nodes, the subpopulations of lymphocytes that interact with metastatic melanoma cells and analyze their associations with outcome, and to determine tumor PD-L1 expression as this may provide a rational scientific basis for the administration of adjuvant anti-PD-1/PD-L1 inhibitors in sentinel lymph node positive metastatic melanoma patients. [Mod Pathol] Abstract

Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T Cells
Researchers investigated the potential of discarded human thymuses, routinely removed during pediatric cardiac surgery, to be used as a novel source of therapeutic regulatory T cells. [Am J Transplant] Abstract

Expression of IL-37 Contributes to the Immunosuppressive Property of Human CD4+CD25+ Regulatory T Cells
Cell surface molecules and secretory cytokines were analyzed in order to determine the function of interleukin-37 (IL-37) in regulating inhibitory effect of human CD4+CD25+ regulatory T cells. [Sci Rep] Full Article

Inhibition of IL-1β-mediated IRAK4 Phosphorylation by Zinc Leads to Repression of Memory Th17 Response in Humans
Scientists examined antibody responses against JC polyomavirus (JCPyV) major capsid protein viral protein 1 variants in the serum and cerebrospinal fluid of healthy donors, JCPyV-positive multiple sclerosis patients treated with the anti-VLA-4 monoclonal antibody natalizumab (NAT), and patients with NAT-associated progressive multifocal leukoencephalopathy. [Immunology] Abstract

Long Noncoding RNA Expression during Human B-Cell Development
Researchers analyzed long noncoding RNA expression during human B-cell development by array-based expression profiling of eleven distinct flow-sorted B-cell subsets, comprising pre-B1, pre-B2, immature, naive, memory, and plasma cells from bone marrow biopsies, and naive, centroblast, centrocyte, memory, and plasmablast cells from tonsil tissue samples, respectively. [PLoS One] Full Article

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies
Scientists examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. [PLoS One] Full Article

The Imbalance between Tregs, Th17 Cells and Inflammatory Cytokines Among Renal Transplant Recipients
Investigators aimed to determine the number of CD4+CD25+Foxp3+ Treg, CD4+IFN-γIL-17+ Th17, CD4+IFN-γ+IL-17 Th1 and CD4+IFN-γ+IL-17+ Th1/17 cells in renal transplant recipients. [BMC Immunol] Full Article

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Novelties in the Management of B-Cell Malignancies: B-Cell Receptor Signaling Inhibitors and Lenalidomide
A plethora of agents including monoclonal antibodies, Bcl-2 antagonists, tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors, mTOR inhibitors and immunomodulatory drugs have been developed in B-cell malignancies. The authors focus on B-cell receptor signaling inhibitors and lenalidomide as an immunomodulatory drug and to provide insight on how and when to incorporate these agents into the treatment algorithms. [Expert Rev Hematol] Abstract

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Breakthrough Study Demonstrates Survival Advantage with Immune Checkpoint Inhibitor for Advanced Kidney Cancer Patients
For the first time, an immune checkpoint inhibitor has been proven to increase survival among patients with advanced renal cell carcinoma, a patient population for whom treatment options are currently limited. [Press release from The University of Texas MD Anderson Cancer Center discussing research presented at the European Cancer Congress (ECC) 2015, Vienna] Press Release

NewLink Genetics Corporation Announces Promising Clinical Data
NewLink Genetics Corporation announced promising early-stage clinical data from a Phase Ia study of GDC-0919, an IDO checkpoint inhibitor being developed in collaboration with Genentech, a member of the Roche Group. [Press release from NewLink Genetics Corporation discussing research presented at the European Cancer Congress (ECC) 2015, Vienna] Press Release

NewLink Genetics Corporation Announces Promising Phase Ib Data from the Combination of Indoximod and Ipilimumab in Melanoma
NewLink Genetics Corporation presented promising early-stage clinical data from a Phase Ib study of indoximod, its wholly owned indoleamine 2,3 dioxygenase (IDO) pathway inhibitor, in combination with ipilimumab for the treatment of patients with unresectable stage 3 or 4 melanoma. [Press release from NewLink Genetics Corporation discussing research presented at the European Cancer Congress (ECC) 2015, Vienna] Press Release

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ImmunoCellular Therapeutics Awarded $19.9 Million Grant from California Institute for Regenerative Medicine (CIRM) to Fund ICT-107 Phase III Registration Program in Glioblastoma
ImmunoCellular Therapeutics, Ltd. announced that the governing Board of the CIRM has awarded the company $19.9 million to support the ICT-107 Phase III registration trial in patients with newly diagnosed glioblastoma. The $19.9 million was granted under the CIRM 2.0 program, a comprehensive collaborative initiative designed to accelerate the development of stem cell-based treatments for people with unmet medical needs. [ImmunoCellular Therapeutics, Ltd.] Press Release

RuiYi Announces the First Human Dosing of a Novel Antibody, Gerilimzumab, for the Treatment of Rheumatoid Arthritis and other Autoimmune Disorders
RuiYi, Inc. announced the first human dosing of Gerilimzumab, a novel monoclonal antibody that is directed against the IL-6 cytokine, for the treatment of autoimmune disorders, including rheumatoid arthritis. [RuiYi, Inc.] Press Release

Neovacs Initiates Phase IIb Trial of IFNα-Kinoid for the Treatment of Lupus
Neovacs announced it has begun enrolling patients in IFN-K-002, a Phase IIb clinical trial to evaluate the efficacy of IFNα-Kinoid, Neovacs’ lead active immunotherapy product candidate, to treat systemic lupus erythematosus. [Neovacs, Inc.] Press Release
National Institutes of Health (United States)

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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 Keystone Symposium – Systems Immunology: From Molecular Networks to Human Biology
January 10-14, 2016
Big Sky, United States

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

NEW Postdoctoral Researcher – Adverse Immune Signatures and their Prevention in Corneal Transplantation (NUI Galway)

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

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

Scientist – Cancer Immunotherapy Discovery (F. Hoffmann-La Roche AG)

Principal Scientist – Translational Medicine (Celgene Corporation)

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))

Faculty Positions – Stem Cell/Immunology/Medical Virology (Hallym University Medical Center)

Research Associate – Cell Biology (Editas Medicine)

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