Volume 3.37 | Sep 22

Human Immunology News 3.37 September 22, 2015
Human Immunology News
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Therapeutic Bispecific T-Cell Engager Antibody Targeting the Intracellular Oncoprotein WT1
The authors describe a bispecific T-cell engager (BiTE) antibody derived from a T-cell receptor-mimic monoclonal antibody ESK1, which binds a peptide derived from the intracellular oncoprotein WT1 presented on human leukocyte antigen-A*02:01. Despite the very low density of the complexes at the cell surface, ESK1-BiTE selectively activated and induced proliferation of cytolytic human T cells that killed cells from multiple leukemias and solid tumors in vitro and in mice. [Nat Biotechnol] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
The Ro60 Autoantigen Binds Endogenous Retroelements and Regulates Inflammatory Gene Expression
Investigators cataloged the Ro60-associated RNAs in human cell lines and found that among other RNAs, Ro60 bound an RNA motif derived from endogenous Alu retroelements. Alu transcripts were induced by type I interferon and stimulated pro-inflammatory cytokine secretion by human peripheral blood cells. [Science] Abstract

TCR-Induced Sumoylation of the Kinase PKC-θ Controls T Cell Synapse Organization and T Cell Activation
Scientists found that the kinase PKC-θ was sumoylated upon costimulation with antigen or via the T cell antigen receptor (TCR) plus the coreceptor CD28, with Lys325 and Lys506 being the main sumoylation sites. Analysis of primary mouse and human T cells revealed that sumoylation of PKC-θ was essential for T cell activation. [Nat Immunol] Abstract

Chimeric Antigen Receptor-Modified T Cells Derived from Defined CD8+ and CD4+ Subsets Confer Superior Antitumor Reactivity In Vivo
Investigators analyzed CD19 CAR-expressing effector T-cells derived from different subsets (CD4+/CD8+ naïve, central memory, effector memory). T-cells derived from each of the subsets were efficiently transduced and expanded, but showed clear differences in effector function and proliferation in vitro and in vivo. [Leukemia] Abstract

Multiple Sclerosis Associated Genetic Variants of CD226 Impair Regulatory T Cell Function
Researchers investigated phenotypical and functional consequences of a genetic variant in the CD226 gene that, among other autoimmune diseases, predisposes to multiple sclerosis. Phenotypically, effector and regulatory CD4+ memory T cells of healthy individuals carrying the predisposing CD226 genetic variant showed, in comparison to carriers of the protective variant, reduced surface expression of CD226 and an impaired induction of CD226 after stimulation. [Brain] Abstract

Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression
With H3K27ac chromatin immunoprecipitation, scientists identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in juvenile idiopathic arthritis patient synovial-fluid-derived CD4+ memory/effector T cells. [Cell Rep] Full Article | Graphical Abstract

Immunological Adaptations to Pregnancy in Women with Type 1 Diabetes
The systemic immune response was assessed by using flow cytometry to evaluate the number and activational status of subpopulations of lymphocytes, natural killer cells and monocytes in peripheral blood of non-pregnant and pregnant women with and without type 1 diabetes. [Sci Rep] Full Article

NK Cells Preferentially Target Tumor Cells with a Cancer Stem Cell Phenotype
Researchers demonstrated that activated NK cells are capable of preferentially killing cancer stem cells (CSCs) identified by multiple CSC markers from a wide variety of human cancer cell lines in vitro and dissociated primary cancer specimens ex vivo. [J Immunol] Abstract

Signal Strength and Metabolic Requirements Control Cytokine-Induced Th17 Differentiation of Uncommitted Human T Cells
Human Th17 cells can be efficiently generated with appropriate cytokines from precommitted precursors, but the requirements of uncommitted T cells are still ill defined. In standard human Th17 cultures, IL-17 production was restricted to CCR6+CD45RA+ T cells, which expressed CD95 and produced IL-17 ex vivo, identifying them as Th17 memory stem cells. [J Immunol] Abstract

Bispecific Antibody Releasing-Mesenchymal Stromal Cell Machinery for Retargeting T Cells towards Acute Myeloid Leukemia Blasts
Researchers examined the use of mesenchymal stromal cells as autonomous cellular machines for the constant production of a recently described, fully humanized anti-CD33-anti-CD3 bispecific antibody, which is capable of redirecting human T cells against CD33-expressing leukemic cells. [Blood Cancer J] Full Article

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The Interplay between Inflammation and Metabolism in Rheumatoid Arthritis
The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine-mediated inflammatory processes in rheumatoid arthritis (RA). The authors review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response. [Cell Death Dis] Full Article

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Penn Team Pinpoints Immune Changes in Blood of Melanoma Patients on PD-1 Drugs that Put Potential Biomarker within Reach
A simple blood test can detect early markers of “reinvigorated” T cells and track immune responses in metastatic melanoma patients after initial treatment with the anti-PD-1 drug pembrolizumab. [Press release from Penn Medicine discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release

Five Prime Therapeutics’ Phase Ia/Ib Trial of FPA008 and OPDIVO (Nivolumab) Featured as a Trial-in-Progress
Five Prime Therapeutics, Inc. announced that the Phase Ia/Ib clinical trial combining FPA008 with OPDIVO® in multiple tumor types was featured in a trial-in-progress poster. [Press release from Five Prime Therapeutics, Inc. discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release

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Caladrius Biosciences and Sanford Research Establish Strategic Collaboration with Goal of Developing Major Advance in Treatment of Type 1 Diabetes
Caladrius Biosciences, Inc. announced that it has entered into a collaboration agreement with Sanford Research to develop the company’s T regulatory cell therapy product candidate, CLBS03, for the treatment of adolescents with recent-onset type 1 diabetes. [Caladrius Biosciences, Inc.] Press Release

Vaccibody AS Announces Vaccination of First Patient in Its Phase I/IIa Study with VB10.16 Immunotherapy for Patients with HPV16 Induced High Grade Lesions of the Cervix
Vaccibody AS announced vaccination of the first patient in its multicenter trial VB C-01 – an exploratory, open-label, multicenter Phase I/IIa study VB10.16 immunotherapy for the treatment of high grade cervical intraepithelial neoplasia caused by human papillomavirus 16 (HPV 16). [Vaccibody AS] Press Release
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European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW 29th Annual Canadian Society for Immunology (CSI) Conference
April 1-4, 2016
Ottawa, Canada

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

NEW 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))

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

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

Research Associate – Cell Biology (Editas Medicine)

Senior Research Associate (Editas Medicine)

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