Volume 3.33 | Aug 25

Human Immunology News 3.33 August 25, 2015
Human Immunology News
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Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
Scientists who analyzed the genes involved in ten autoimmune diseases that begin in childhood have discovered 22 genome-wide signals shared by two or more diseases. These shared gene sites may reveal potential new targets for treating many of these diseases, in some cases with existing drugs already available for non-autoimmune disorders. [Press release from The Children’s Hospital of Philadelphia discussing online prepublication in Nature Medicine] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Out-of-Sequence Signal 3 Paralyzes Primary CD4+ T-Cell-Dependent Immunity
Scientists showed that during strong stimulation, a profound suppression of primary CD4+ T-cell-mediated immune responses ensued and was observed across preclinical models and patients undergoing high-dose interleukin-2 therapy. These events resulted in complete paralysis of primary CD4+ T cell activation, affecting memory generation and induction of autoimmunity as well as impaired viral clearance. [Immunity]
Abstract | Graphical Abstract | Press Release

High-Throughput Pairing of T Cell Receptor α and β Sequences
Researchers describe and validate a method called pairSEQ, which can leverage the diversity of T cell receptor (TCR) sequences to accurately pair hundreds of thousands of TCR α and TCR β sequences in a single experiment. [Sci Transl Med] Abstract | Press Release

Immunosuppressive Human Anti-CD83 Monoclonal Antibody Depletion of Activated Dendritic Cells in Transplantation
Investigators developed a human IgG1 monoclonal antibody (mAb), 3C12, specific for CD83, which is expressed on activated but not resting dendritic cells. The 3C12 mAb and an affinity improved version, 3C12C, depleted CD83+ cells by CD16+ NK cell mediated antibody dependent cellular cytotoxicity, and inhibited allogeneic T cell proliferation in vitro. [Leukemia] Abstract

Extracellular Signal–Regulated Kinase 5 Promotes Acute Cellular and Systemic Inflammation
Researchers inhibited the kinase activities and reduced the abundances of extracellular signal–regulated kinase 5 (ERK5) and MEK5, a mitogen-activated protein kinase kinase directly upstream of ERK5, in primary human vascular endothelial cells and monocytes, and found that ERK5 promoted inflammation induced by a broad range of microbial Toll-like receptor agonists and by the proinflammatory cytokines interleukin-1β and tumor necrosis factor‑α. [Sci Signal] Abstract

Activated and Expanded Natural Killer Cells Target Osteosarcoma Tumor Initiating Cells in an NKG2D–NKG2DL Dependent Manner
Scientists explored the efficacy and the pathways involved in natural killer (NK) cells’ elimination of osteosarcoma (OS) cells, including tumor initiating cells, which are responsible for chemotherapy resistance, recurrence, and metastasis. They found OS cells were susceptible to activated and expanded NK cells’ lysis both in vivo and in vitro, and this cytolytic activity relied on interaction between NKG2D receptor and NKG2D ligands (NKG2DL). [Cancer Lett] Abstract

Age-Related Profiling of DNA Methylation in CD8+ T Cells Reveals Changes in Immune Response and Transcriptional Regulator Genes
Researchers studied age-related changes in DNA methylation and gene expression in CD4+ and CD8+ T cells from younger and older individuals. They observed marked difference between T cell subsets, with increased number of methylation changes and higher methylome variation in CD8+ T cells with age. [Sci Rep] Full Article

Glycosylation-Dependent Interaction between CD69 and S100A8/S100A9 Complex Is Required for Regulatory T-Cell Differentiation
By RNA interference, investigators showed that CD69 is not sufficient to support the conversion of CD4+ naive T cells into regulatory T cells, whereas it does that of human peripheral blood mononuclear cells, suggesting that a ligand-receptor interaction is required for CD69 function. [FASEB J] Abstract

TLR3 Drives IRF6-Dependent IL-23p19 Expression and p19/EBI3 Heterodimer Formation in Keratinocytes
Investigators report that interferon regulatory factor (IRF) regulates a subset of Toll-like receptor (TLR)3 responses in human keratinocytes, including the production of a novel interleukin-12 (IL-12) family heterodimer (p19/EBI3). They propose that the TLR3-IRF6-p19/EBI3 axis may regulate keratinocyte and/or immune cell functions in the context of cell damage and wound healing in the skin. [Immunol Cell Biol] Full Article

Expression of TNFR2 by Regulatory T Cells in Peripheral Blood Is Correlated with Clinical Pathology of Lung Cancer Patients
The authors investigated the phenotype and function of tumor necrosis factor receptor type II (TNFR2)+ regulatory T cells (Tregs) present in the peripheral blood of 43 lung cancer patients. Further, the association of TNFR2 expression on Tregs with clinicopathological factors was analyzed. [Cancer Immunol Immunother] Abstract

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The Genomic Landscape of Human Immune-Mediated Diseases
The authors review the genomic landscape of immune-mediated diseases and analyze overlapping loci between diseases. There may be a need for more epigenetics studies to aid in the understanding of the transition from genotype to phenotype. [J Hum Genet] Abstract

Associations of Human Leukocyte Antigens with Autoimmune Diseases: Challenges in Identifying the Mechanism
Scientists summarize what is currently known about the mechanisms of human leukocyte antigen (HLA) associations with rheumatoid arthritis and type 1 diabetes, and elucidate the potential mechanistic basis of the HLA–autoimmunity associations. [J Hum Genet] Abstract

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Transgene Announces Oral Presentation on TG4010 Cancer Immunotherapy at World Conference on Lung Cancer
Transgene S.A. announced that results, including more mature overall survival data, from the Phase IIb part of the Phase IIb/III TIME trial with its immunotherapy candidate TG4010 in non-small cell lung cancer, will be presented. [Press release from Transgene S.A. discussing research to be presented at the 16th World Conference on Lung Cancer, Denver] Press Release

Immunicum Updates Safety and Survival Data in Phase I/II Liver Cancer Study with INTUVAX
Immunicum AB released an updated report on safety and survival data from the ongoing Phase I/II study with INTUVAX for patients with primary liver cancer. Of a total of seven fully treated patients, four showed a prolonged survival as compared to expected based on historical data. [Immunicum AB] Press Release

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AstraZeneca and Peregrine Pharmaceuticals to Collaborate on Immuno-Oncology Combination Clinical Trial
AstraZeneca and Peregrine Pharmaceuticals, Inc. announced that they have entered into a cancer immunotherapy clinical trial collaboration. The collaboration will evaluate Peregrine’s investigational phosphatidylserine-signaling pathway inhibitor, bavituximab, in combination with AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab. [Peregrine Pharmaceuticals, Inc.] Press Release

TxCell Consortium Granted €1.28 Million for TRUST Project on Process and Clinical Development of Col-Treg for Autoimmune Uveitis Treatment
TxCell SA announced that the French government’s Unique Interministerial Fund has granted €1.28 million to the TRUST project (TRegs in Uveitis STudy). The TRUST project will be run by a consortium headed by TxCell and will be dedicated to process and clinical development of Col-Treg, TxCell’s second lead product, for the treatment of autoimmune uveitis. [TxCell SA] Press Release

Ocata Therapeutics Receives SBIR Grant from NIH to Develop Proprietary Hemangio-Derived Mesenchymal Cell Therapy for Lupus Nephritis
Ocata Therapeutics, Inc. announced that it has been awarded a Small Business Innovation Research (SBIR) Phase I grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), to fund further preclinical development of Ocata’s proprietary hemangio-derived mesenchymal cell product for the treatment of systemic lupus erythematosus and lupus nephritis. [Ocata Therapeutics, Inc.] Press Release

Esperite Acquires Patent to Use MSC-Derived Exosomes for Broad Applications in Immunology
Esperite has acquired the full rights of a broad international patent enabling MSC-derived exosomes use in treatment of inflammatory and autoimmune diseases. Esperite is positioned to spearhead advances in treatment for graft versus host disease after solid organ and cell transplantations, Crohn’s disease, arthritis, multiple sclerosis, cystic fibrosis, stroke, traumatic brain and spinal cord injury, newborn encephalopathy, and type 1 diabetes among others. [Esperite N.V.] Press Release

Advaxis and MedImmune Commence Enrollment in Phase I/II Study of Axalimogene Filolisbac (ADXS-HPV) in Combination with Durvalumab (MEDI4736) for the Treatment of HPV-Associated Cancers
Advaxis, Inc. and MedImmune announced that enrollment has commenced in a Phase I/II clinical trial of ADXS-HPV, Advaxis’s investigational Lm Technology™ immunotherapy, in combination with MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab, for the treatment of patients with advanced, recurrent or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer. [Advaxis, Inc.] Press Release
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NEW The 15th International Conference on Progress in Vaccination against Cancer (PIVAC-15)
October 6-8, 2015
Tübingen, Germany

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

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Senior Research Technician (Qu Biologics Inc.)

Postdoctoral Research Fellow – Development and Pathogenesis of Pancreatic Cancer (University College London)

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

Postdoctoral Fellow – Biotechnology (Qu Biologics Inc.)

Harry Eagle Scholar Awards for Postdoctoral Candidates (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Positions – Cancer Research (Rutgers University)

Research Associate – Cell Biology (Editas Medicine)

Senior Research Associate (Editas Medicine)

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

Postdoctoral Fellow – Immunology (Cellectis Inc.)

Postdoctoral Fellowship – Immunology (Huazhong University of Science and Technology)

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