Human Immunology News Volume 3.23 | Jun 16 2015

Genetic Variants Associated with Autoimmunity Drive NFκB Signaling and Responses to Inflammatory Stimuli
Scientists demonstrate that genetic variants associated with risk of developing multiple sclerosis alter NFκB signaling pathways, resulting in enhanced nuclear factor κB (NFκB) activation and greater responsiveness to inflammatory stimuli. [Sci Transl Med] Abstract | Press Release

A Novel Mechanism of Generating Extracellular Vesicles during Apoptosis via a Beads-on-a-String Membrane Structure
While observing monocytes undergoing apoptosis by time-lapse microscopy, researchers discovered a new type of membrane protrusion that resembles a ‘beads-on-a-string’ structure. Strikingly, the ‘beads’ are frequently sheared off the ‘string’ to form apoptotic bodies. [Nat Commun] Full Article | Press Release | Video

Neutralization and Clearance of GM-CSF by Autoantibodies in Pulmonary Alveolar Proteinosis
Investigators characterized 21 GM-CSF autoantibodies from pulmonary alveolar proteinosis patients and found that somatic mutations critically determine their specificity for the self-antigen. [Nat Commun] Full Article

Latent Membrane Protein LMP2A Impairs Recognition of EBV-Infected Cells by CD8⁺ T Cells
Researchers infected primary B cells with Epstein-Barr virus (EBV) deleted for latent membrane protein 2A (LMP2A), and established lymphoblastoid cell lines (LCLs). They found that CD8⁺ T cell clones showed higher reactivity against LMP2A-deficient LCLs compared to LCLs infected with complete EBV. They identified several potential mediators of this immunomodulatory effect. [PLoS Pathog] Full Article | Press Release

Mapping the Diversity of Follicular Helper T Cells in Human Blood and Tonsils Using High-Dimensional Mass Cytometry Analysis
Investigators applied dimensionality reduction and automated clustering methods on human T helper (T_H) cells derived from peripheral blood and tonsils, which showed differential cell composition and extensive T_H cell heterogeneity. Notably, this analysis revealed numerous subtypes of follicular helper T cells that followed a continuum spanning both blood and tonsils. [Cell Rep] Full Article | Graphical Abstract

Analysis of Single-Cell Cytokine Secretion Reveals a Role for Paracrine Signaling in Coordinating Macrophage Responses to TLR4 Stimulation
To determine the role of paracrine signaling in shaping the profile of inflammatory cytokines secreted by macrophages in response to stimulation of Toll-like receptor 4 (TLR4) with lipopolysaccharide, researchers combined multiplexed, microwell-based measurements of cytokine secretion by single cells with analysis of cytokine secretion by cell populations. [Sci Signal] Abstract

Androgen Receptor Modulates Foxp3 Expression in CD4⁺CD25⁺Foxp3⁺ Regulatory T-Cells
Scientists showed a significant androgen-dependent increase of Foxp3 expression in human T-cells from females in the ovulatory phase of the menstrual cycle, but not from males and identify a functional androgen response element within the Foxp3 locus. [Mol Biol Cell] Abstract | Full Article

Measles Virus Hemagglutinin Triggers Intracellular Signaling in CD150-Expressing Dendritic Cells and Inhibits Immune Response
Scientists analyzed the effect of measles virus hemagglutinin interaction with CD150-expressing dendritic cells (DCs) on the DC signaling pathways and consequent phenotypic and functional changes in the absence of infectious context. [Cell Mol Immunol] Abstract

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Principia Biopharma Presents Full Phase I Clinical Trial Results for PRN1008, a Novel Reversible Covalent BTK Inhibitor, Supporting further Clinical Development in Autoimmune and Inflammatory Diseases
Results showed that PRN1008 was well tolerated after single and ten-day dosing and demonstrated sustained therapeutic levels of Burton’s tyrosine kinase (BTK) receptor occupancy following a brief period of systemic drug exposure. [Press release from Principia Biopharma Inc. discussing research presented at the European League Against Rheumatism (EULAR) 2015 Annual Meeting, Rome] Press Release

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ImmunoCellular Therapeutics Enters into Manufacturing Agreement with PCT LLC, a Caladrius Company, for US Production of ICT-107 for Phase III Registration Trial
ImmunoCellular Therapeutics, Ltd. announced the selection of PCT, LLC as the US manufacturer for ImmunoCellular’s ICT-107 Phase III registrational clinical program in newly diagnosed glioblastoma. Under the terms of the multi-year agreement, PCT will provide current good manufacturing practice services for the manufacture of clinical supplies of ICT-107, a dendritic cell-based immunotherapy targeting six tumor-associated antigens. [ImmunoCellular Therapeutics, Ltd.] Press Release

Prothena Announces First Human Dosed in Phase I Study of PRX003 for the Treatment of Psoriasis and Other Inflammatory Diseases
Prothena Corporation plc announced the successful first human dosing in a Phase I clinical trial of its proprietary protein immunotherapy, PRX003. PRX003 is a monoclonal antibody targeting melanoma cell adhesion molecule for the potential treatment of psoriasis and other inflammatory diseases. [Prothena Corporation plc] Press Release

Advaxis Submits Special Protocol Assessment Request to FDA for ADXS-HPV Phase III Clinical Trial in Cervical Cancer
Advaxis, Inc. announced the company has submitted a Special Protocol Assessment request to the U.S. Food and Drug Administration (FDA) to initiate detailed design discussions for a Phase III clinical study of ADXS-HPV for the treatment of high-risk, locally advanced cervical cancer. [Advaxis, Inc.] Press Release

Ludwig Cancer Research Expands Presence in Lausanne
Ludwig Cancer Research announced that it is opening a new Branch in Lausanne, Switzerland. The Branch will be focused primarily on applied cancer immunology and the design of novel molecular and cell-based immunotherapies. [Ludwig Cancer Research] Press Release

STEMCELL Technologies Named Company of the Year by BIOTECanada
STEMCELL Technologies Inc. will be presented with the Biotech Company of the Year award by BIOTECanada at this year’s BIO International Convention in Philadelphia. [BIOTECanada] Press Release

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

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Scientific Marketing Specialist – Immunology (STEMCELL Technologies Inc.)

PhD Position – Molecular Immunology (VIB – Ghent University)

Head Stem Cells Immunotherapies Service Lab (NHS Blood and Transplant)

Postdoctoral Fellow – Immune Reconstitution in Hematopoietic Stem Cell Transplantation (Stanford University)

Postdoctoral Fellow – Immune Tolerance (Stanford University)

Research Scientist – Immunology (Gilead Sciences)

PhD Position – Microbial Immunology (Hans Knöll Institute)

Process Facilitator (Opexa Therapeutics)

Scientist – Immunology Discovery (Genentech, Inc.)

Postdoctoral Position – Immunology (University of California, San Francisco)

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