Volume 3.09 | Mar 10

Human Immunology News 3.09 March 10, 2015
Human Immunology News
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Human Monocytes Undergo Functional Re-Programming during Sepsis Mediated by Hypoxia-Inducible Factor-1α
Investigators performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Their results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. [Immunity] Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Toxicity of Eosinophil MBP Is Repressed by Intracellular Crystallization and Promoted by Extracellular Aggregation
Investigators showed how intragranular major basic protein (MBP-1) nanocrystals restrain toxicity, enabling its safe storage, and characterized them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity was triggered by granule acidification, followed by extracellular aggregation, which mediated the damage to pathogens and host cells. [Mol Cell] Abstract | Graphical Abstract

Mucosal-Associated Invariant T Cell Alterations in Obese and Type 2 Diabetic Patients
Scientists analyzed mucosal-associated invariant T (MAIT) cells in the blood and adipose tissues of patients with type 2 diabetes and/or severe obesity. In both patient groups, circulating MAIT cells displayed an activated phenotype that was associated with elevated Th1 and Th17 cytokine production. [J Clin Invest]
Full Article | Press Release

Use of the CRISPR/​Cas9 System as an Intracellular Defense against HIV-1 Infection in Human Cells
Investigators adapted the CRISPR/​Cas9 system to human cells for intracellular defense against foreign DNA and viruses. Using HIV-1 infection as a model, their results demonstrate that the CRISPR/​Cas9 system disrupts latently integrated viral genome and provides long-term adaptive defense against new viral infection, expression and replication in human cells. [Nat Commun] Abstract | Press Release

Human Ebola Virus Infection Results in Substantial Immune Activation
Researchers characterized the human immune response to Ebola virus infection in four patients. They defined the kinetics of T- and B-cell activation, and determined which viral proteins are targets of the Ebola virus-specific T-cell response in humans. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

L-Selectin Shedding Is Activated Specifically within Transmigrating Pseudopods of Monocytes to Regulate Cell Polarity In Vitro
Using advanced imaging techniques, scientists observed L-selectin shedding occurring exclusively as primary human monocytes actively engage in transendothelial migration. Moreover, the shedding was localized to transmigrating pseudopods within the subendothelial space. [Proc Natl Acad Sci USA] Abstract | Full Article

An Autologous Endothelial Cell: Peripheral Blood Mononuclear Cell Assay that Detects Cytokine Storm Responses to Biologics
Investigators report a novel bioassay where endothelial cells grown from stem cells in the peripheral blood and peripheral blood mononuclear cells from the same donor can be used to create an autologous coculture bioassay that responds by releasing a plethora of cytokines to authentic TGN1412 but only modestly to Campath and not to control antibodies such as Herceptin, Avastin, and Arzerra. [FASEB J]
Abstract | Press Release

A Discrete Population of IFN λ-Expressing BDCA3hi Dendritic Cells Is Present in Human Thymus
Researchers describe in human thymus the presence of a discrete population of BDCA3hi dendritic cells that, like their peripheral counterparts, express CD13, low-intermediate levels of CD11c, CLEC9A, high levels of XCR1, IRF8 and TLR3, and mostly lack the expression of CD11b, CD14 and TLR7. [Immunol Cell Biol] Abstract

Complement Receptor Type 1 (CR1/CD35) Expressed on Activated Human CD4+ T Cells Contributes to Generation of Regulatory T Cells
Researchers demonstrated that co-ligation of CD46 and CD35, the two C3b-binding structures present on activated CD4+ human T cells significantly enhanced CD25 expression, elevated granzyme B production and synergistically augmented cell proliferation. [Immunol Lett] Abstract

Linezolid, Vancomycin and Daptomycin Modulate Cytokine Production, Toll-Like Receptors and Phagocytosis in a Human In Vitro Model of Sepsis
Scientists examined the effect of antibiotics linezolid (LIN), vancomycin (VAN) and daptomycin (DAP) on the immune response under sepsis-like conditions in vitro. Lipopolysaccharide-activated THP-1 monocytes were incubated with LIN, VAN or DAP. The antibiotics differentially modulated the gene expression of investigated cytokines. [J Antibiot] Full Article

Human Leukocyte Antigen (HLA) A*1101-Restricted Epstein-Barr Virus-Specific T-Cell Receptor Gene Transfer to Target Nasopharyngeal Carcinoma
Scientists explored T-cell receptor (TCR) gene transfer to rapidly and reliably generate T-cells specific for the nasopharyngeal carcinoma-associated viral protein LMP2. Studying both wild-type and modified forms they optimized expression of the TCR and demonstrated high avidity antigen-specific function in both CD8+ and CD4+ T-cells. [Cancer Immunol Res] Abstract | Press Release

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March Magnet Maddness: Free EasySep™ Magnet with Purchase of Cell Isolation Reagents
Balancing Natural Killer Cell Activation through Paired Receptors
The authors focus on the recent advances in the understanding of how receptors regulate natural killer (NK) cell biology and of their roles in pathologies such as cancer, infection and autoimmunity. [Nat Rev Immunol] Abstract

Inflammation-Induced Foam Cell Formation in Chronic Inflammatory Disease
Two models describe early events initiating atherosclerotic plaque formation, whereby foam cells form in response to hyperlipidaemia or inflammation-associated stimuli. The authors assess the role of monocytes in each model and discuss how key steps in atherogenesis may be targeted to enhance clinical outcomes in patients with chronic inflammatory disease. [Immunol Cell Biol] Abstract

Beyond Consolidation: Auto-SCT and Immunotherapy for Plasma Cell Myeloma
Investigators discuss the preclinical data supporting immunotherapy in autologous hematopoietic cell transplantation for myeloma, clinical investigation of these strategies and the future prospects of immunotherapy in pursuit of the goal of curative therapy. [Bone Marrow Transplant] Abstract

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Biothera’s Investigational Cancer Immunotherapy Imprime PGG Neutralizes Cancer Defense Mechanisms in the Tumor Microenvironment
New preclinical research from Biothera further demonstrates the ability of its cancer immunotherapy drug candidate Imprime PGG® to initiate a cascade effect of immune responses that neutralize cancer-associated immunosuppression in the tumor microenvironment. [Press release from Biothera discussing research presented at the Keystone Symposium: Dendritic Cells and Macrophages Reunited, Montreal]
Press Release | Poster

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CPRIT Awards Faculty $11.5 Million for Recruitment and Research in Brain and Bone Cancer, Biology, and Immunotherapy
The Cancer Prevention and Research Institute of Texas (CPRIT) has awarded UT Southwestern Medical Center researchers more than $7.5 million in research grants to improve diagnostic and therapeutic services and research relating to cancers of the brain, breast, throat, and bone, as well as to improve scientific understanding of cancer biology. UT Southwestern received an additional $4 million for recruiting emerging cancer scientists. [UT Southwestern Medical Center] Press Release

Opexa Amends Agreement with Merck Serono and Receives Additional $3 Million Payment to Support Ongoing Development of Tcelna® for Multiple Sclerosis
Opexa Therapeutics, Inc. announced that it has amended its option and license agreement with Merck Serono and will receive a $3 million payment. The payment provides support for the ongoing Phase IIb clinical study of Tcelna® as well as the preparation and planning of potential Phase III studies. [Opexa Therapeutics, Inc.] Press Release

FDA Approves Opdivo (Nivolumab) for the Treatment of Patients with Previously Treated Metastatic Squamous Non-Small Cell Lung Cancer
Bristol-Myers Squibb Company announced that the U.S. Food and Drug Administration (FDA) has approved Opdivo injection, for intravenous use, for the treatment of patients with metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy. [Bristol-Myers Squibb Company] Press Release

Takeda Announces Transfer of License Agreement for Human Papillomavirus (HPV) Vaccine to Kaketsuken
Takeda Pharmaceutical Company Limited announced that it has transferred its license agreement with the Japan Health Sciences Foundation for worldwide patent rights of a HPV vaccine to the Chemo-Sero-Therapeutic Research Institute (Kaketsuken). [Takeda Pharmaceutical Company Limited] Press Release

ORYX Successfully Completes Phase I/IIa Trial with Therapeutic Vaccine VicOryx to Treat HPV-Associated Cancers
ORYX announced the successful completion of a Phase I/IIa trial of the therapeutic vaccine VicOryx to treat p16INK4a-overexpressing HPV- (human papilloma virus-) positive cancer patients in an open label, single center trial that included 26 patients. [ORYX] Press Release
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June 7-12, 2015
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NEW Manufacturing Manager – Cell Therapy (Opexa Therapeutics)

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

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Postdoctoral Fellowship – Human Immunology (University of Pennsylvania)

Postdoctoral Scientist – Immunology (University of Oxford)

Postdoctoral Position – Immunology (The Broad Institute of MIT and Harvard)

Faculty Position – Immunology (The Lowance Center for Human Immunology at Emory University)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Director – Vector Production (Sangamo BioSciences, Inc.)

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