Immune Regulation News Volume 7.06 | Feb 20 2015

The Chromatin-Modifying Enzyme Ezh2 Is Critical for the Maintenance of Regulatory T Cell Identity after Activation
Scientists showed that CD28 co-stimulation, an extracellular cue intrinsically required for regulatory T (Treg) cell maintenance, induced the chromatin-modifying enzyme, Ezh2. Treg-specific ablation of Ezh2 resulted in spontaneous autoimmunity with reduced Foxp3⁺ cells in non-lymphoid tissues and impaired resolution of experimental autoimmune encephalomyelitis. [Immunity] Abstract | Graphical Abstract

Rational Development and Characterization of Humanized Anti-EGFR Variant III Chimeric Antigen Receptor T Cells for Glioblastoma
Investigators generated a panel of humanized single-chain variable fragments (scFvs) and tested their specificity and function as soluble proteins and in the form of chimeric antigen receptor (CAR)-transduced T cells. Lead candidate scFv was tested in vitro for its ability to direct CAR-transduced T cells to specifically lyse, proliferate, and secrete cytokines in response to antigen-bearing targets. [Sci Transl Med]
Abstract | Press Release

Normalization of CD4⁺ T Cell Metabolism Reverses Lupus
CD4⁺ T cells rely on glycolysis for inflammatory effector functions, but recent studies have shown that mitochondrial metabolism supports their chronic activation. Researchers show that both glycolysis and mitochondrial oxidative metabolism are elevated in CD4⁺ T cells from lupus-prone B6.Sle1.Sle2.Sle3 mice as compared to non-autoimmune controls. [Sci Transl Med] Abstract

Dendritic Cells Induce Th2-Mediated Airway Inflammatory Responses to House Dust Mite via DNA-Dependent Protein Kinase
Investigators demonstrate that pharmacological inhibition of DNA-dependent protein kinase (DNA-PK), as well as the specific deletion of DNA-PK in dendritic cells, attenuates the induction of allergic sensitization and Th2 immunity via a mechanism that involves the impaired presentation of mite antigens. [Nat Commun] Abstract

Defined ​TLR3-Specific Adjuvant that Induces NK and CTL Activation without Significant Cytokine Production In Vivo
Scientists created an RNA ligand for ​Toll-like receptor 3 (TLR3) with no ability to activate the ​RIG-I/​MDA5 pathway. The activation of ​TLR3/​TICAM-1 pathway by phosphorothioate ODN-guided dsRNA effectively induced natural killer (NK) and cytotoxic T cells in tumor-loaded mice, establishing antitumor immunity. [Nat Commun] Abstract

Self-Restrained B Cells Arise following Membrane IgE Expression
Scientists demonstrate a self-controlled membrane immunoglobulin E (mIgE)⁺ B cell stage. Primary or transfected mIgE⁺ cells relocate the B cell receptors into spontaneously internalized lipid rafts, lose mobility to chemokines, and change morphology. [Cell Rep] Full Article | Graphical Abstract | Press Release

Estrogen Regulates T Helper 17 Phenotype and Localization in Experimental Autoimmune Arthritis
Researchers investigated the effects of estrogen on interleukin-17-producing T helper (Th17) cells in experimental arthritis. They report that 17β-estradiol treatment results in an increase of Th17 cells in lymph nodes during the early phase of arthritis development, but a decrease of Th17 in joints during established arthritis. [Arthritis Res Ther] Abstract | Full Article

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Humanized Models of Tumor Immunology in the 21^st Century: Convergence of Cancer Research and Tissue Engineering
Investigators provide an overview of the state of the art of humanized models of tumor immunology and highlight future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems. [Stem Cells] Abstract

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Celsion Corporation Presents Clinical and Preclinical Data for GEN-1 IL-12 Immunotherapy in Ovarian Cancer
Celsion Corporation presented clinical and preclinical data demonstrating the safety, biological activity and clinical benefits of GEN-1, its DNA-based immunotherapy, as a single agent in advanced platinum-resistant and recurrent ovarian cancer patients. [Press release from Celsion Corporation discussing research presented at the Molecular Medicine TRI-Conference, San Francisco] Press Release | Presentation

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Sanofi and Lead Pharma to Develop Treatments for Autoimmune Diseases
Sanofi announced that it has entered into a research collaboration and license agreement with Dutch biotech Lead Pharma to discover, develop and commercialize small-molecule therapies directed against the nuclear hormone receptors called RORγt to treat a broad range of autoimmune disorders, including rheumatoid arthritis, psoriasis and inflammatory bowel disease, which are among the most common. [Sanofi] Press Release

FDA Grants Genentech’s Cobimetinib Priority Review for Use in Combination with Zelboraf (Vemurafenib) in Advanced Melanoma
Genentech announced the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for the company’s New Drug Application for cobimetinib in combination with Zelboraf^® for the treatment of people with BRAF V600 mutation-positive advanced melanoma. [Kite Pharma, Inc.] Press Release

Immunicum Receives Approval to Start Phase II Study with the Therapeutic Cancer Vaccine INTUVAX
Immunicum AB announced that the Swedish Medical Products Agency has granted the company’s application to commence a Phase II clinical trial in patients with renal cell carcinoma with the therapeutic cancer vaccine INTUVAX in Sweden. [Immunicum AB] Press Release

Food and Drug Administration (United States)

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)

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NEW Postdoctoral Researcher – Tumor Immunology and Immunotherapy (Cleveland Clinic Lerner Research Institute)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

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

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Postdoctoral Associate – Oligonucleotide Aptamer-Based Compounds to Protect Tumor Vaccine-Induced Immune Cells (University of Miami)

Director – Vector Production (Sangamo BioSciences, Inc.)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Assistant/Associate Professor – Gastroenterology (North Carolina State University College of Veterinary Medicine)

Postdoctoral Fellowship – CNS Inflammation (Rutgers University)

Postdoctoral Position – HIV and Ebolavirus (University of Missouri)

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