Immune Regulation News Volume 11.36 | Sep 27 2019

TOP STORY

In Vivo CRISPR Screening in CD8 T Cells with AAV-Sleeping Beauty Hybrid Vectors Identifies Membrane Targets for Improving Immunotherapy for Glioblastoma

Researchers performed in vivo adeno-associated virus (AAV)-Sleeping Beauty-CRISPR screens for membrane protein targets in CD8⁺ T cells in mouse models of glioblastoma (GBM). They validated screen hits by demonstrating that adoptive transfer of CD8⁺ T cells with Pdia3, Mgat5, Emp1 or Lag3 gene editing enhances the survival of GBM-bearing mice in both syngeneic and T-cell receptor transgenic models. [Nat Biotechnol] Abstract

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An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer

A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 that mediated coordinated transcriptional silencing of the MHC class I antigen processing pathway, promoting evasion of T cell-mediated immunity. [Cancer Cell] Full Article | Graphical Abstract

CAR T Cells Targeting BAFF-R Can Overcome CD19 Antigen Loss in B Cell Malignancies

The authors developed humanized, second-generation CAR T cells against another B cell-specific marker, B cell activating factor receptor (BAFF-R), which demonstrated cytotoxicity against human lymphoma and acute lymphoblastic leukemia lines. [Sci Transl Med] Full Article

IFN-γ Enhances Cell-Mediated Cytotoxicity against Keratinocytes via JAK2/STAT1 in Lichen Planus

Using global transcriptomic profiling of patient skin samples, investigators demonstrated that lichen planus was characterized by a type II interferon (IFN) inflammatory response. [Sci Transl Med] Abstract

Tissue-Resident Memory CD8⁺ T Cells Amplify Anti-Tumor Immunity by Triggering Antigen Spreading through Dendritic Cells

Scientists showed that antigen-specific activation of skin tissue-resident memory CD8⁺ T cells led to maturation and migration to draining lymph nodes of cross-presenting dermal dendritic cells. [Nat Commun] Full Article

CXCR5⁺PD-1⁺ Follicular Helper CD8 T Cells Control B Cell Tolerance

Investigators report a CXCR5⁺PD1⁺ T follicular helper subset of CD8⁺ T cells whose development and function were negatively modulated by Stat5. [Nat Commun] Full Article

T-Cell Receptor Signal Strength and Epigenetic Control of Bim Predict Memory CD8⁺ T-Cell Fate

The authors report, using a novel Bim-mCherry knock-in mouse, that cells with high levels of Bim preferentially developed into “central” memory T cells. Bim levels remained stable and were regulated by DNA methylation at the Bim promoter. [Cell Death Differ] Full Article

GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-Tumor Responses

Scientists demonstrated that chemotherapy capable of microtubule destabilization has direct effects on dendritic cell (DC) function; namely, it induces potent DC maturation and elicits anti-tumor immunity. [Cell Rep] Full Article | Graphical Abstract

DAPK1 (Death Associated Protein Kinase 1) Mediates mTORC1 Activation and Antiviral Activities in CD8⁺ T Cells

Researchers showed that both the kinase activity and the death domain of DAPK1 were required for maximal mechanistic target of rapamycin (mTOR) activation and CD8⁺ T-cell function. [Cell Mol Immunol] Abstract

Role of NF-kappaB2-p100 in Regulatory T Cell Homeostasis and Activation

Investigators showed that mice deficient in the non-canonical NF-κB component gene Nfkb2 (p100) had normal thymic development and suppressive function of Tregs. [Sci Rep] Full Article

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The tRNA‐Associated Dysregulation in Immune Responses and Immune Diseases

The authors address recent advances in different aspects of tRNA‐associated dysregulation in immune responses, such as tRNA molecules, tRNA modifications, tRNA derivatives and tRNA aminoacylation. [Acta Physiol] Abstract

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Harvard University Establishes mRNA Immunotherapy Research Collaboration with Moderna

Harvard University has established a multi-year research collaboration Moderna, Inc. with the goal of identifying and developing novel therapeutic approaches that could improve the lives of patients with immunological diseases. [Harvard University] Press Release

Rigel’s Fostamatinib Enters Phase III Clinical Trial in Japan with Kissei Pharmaceuticals for the Treatment of Chronic Immune Thrombocytopenia

Rigel Pharmaceuticals, Inc. announced that its collaboration partner, Kissei Pharmaceuticals Co., Ltd., has initiated a Phase III trial in Japan of fostamatinib disodium hexahydrate in adult patients with chronic immune thrombocytopenia. [Rigel Pharmaceuticals, Inc.] Press Release

Menlo Therapeutics Announces Completion of Enrollment of 233 Patients in Phase II Trial of Serlopitant in Patients with Chronic Pruritus of Unknown Origin

Menlo Therapeutics Inc. announced that it has completed patient enrollment in its Phase II clinical trial evaluating the safety and efficacy of once daily oral serlopitant for the treatment of chronic pruritus of unknown origin. [Menlo Therapeutics Inc.] Press Release

Annexon Biosciences Announces FDA Fast Track Designation for Novel C1q Inhibitor ANX005 for the Treatment of Guillain-Barré Syndrome

Annexon Biosciences announced that the FDA has granted Fast Track designation for ANX005 for the treatment of Guillain-Barré Syndrome, a rare, acute, antibody-mediated autoimmune disease impacting the peripheral nervous system for which there are currently no approved therapies in the United States. [Annexon Biosciences (Business Wire, Inc.)] Press Release

Celsius Therapeutics Signs Multiple Agreements with Academic Institutions to Access Samples for the Identification of Novel Targets in Immune Checkpoint Therapy Resistance

Celsius Therapeutics announced the signing of collaboration agreements with the Parker Institute for Cancer Immunotherapy, Institut Gustave Roussy and the University Health Network. [Celsius Therapeutics] Press Release

FDA Grants Breakthrough Therapy Designation for Roche’s Gazyva (Obinutuzumab) in Lupus Nephritis

Roche announced that the FDA has granted Breakthrough Therapy Designation to Gazyva^® for adults with lupus nephritis. [F. Hoffmann-La Roche Ltd] Press Release

Tarsius Pharma Announces FDA Acceptance of IND Application for TRS01

Tarsius Pharma announced the acceptance of its Investigational New Drug (IND) application for TRS01 by the FDA. [Tarsius Pharma (PR Newswire Association LLC)] Press Release

United States Patent and Trademark Office Issues Innate Biologics™ E3 Ligase Effector Protein Patent

Innate Biologics™ has been granted patent protection for its novel E3 Ligase recombinant protein platform that targets inflammatory signaling pathways. [Innate Biologics™ (Business Wire, Inc.)] Press Release

NIH Reveals Its Formula for Tracking Foreign Influences

The US National Institutes of Health (NIH) thinks it may have figured out how China’s foreign talents recruitment program is undermining its system for making awards and ensuring ethical behavior by its grantees. [ScienceInsider] Editorial

How Us Sanctions Are Crippling Science in Iran

After almost a year of sanctions put in place by US President Donald Trump, Iran is experiencing economic recession, a depreciating currency and high inflation. All of this is stretching budgets for equipment, supplies and travel, endangering research projects and sapping morale, say researchers. [Nature News] Editorial

The Potent Effects of Japan’s Stem-Cell Policies

A five-year regulatory free-for-all in regenerative medicine has given the industry a boost. But patients might be paying the price. [Nature News] Editorial

NEW Stromal Cells in Immunity and Disease
February 19-23, 2020
Victoria, British Columbia, Canada

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NEW Postdoctoral Research Associate – Innate Immune Signaling Pathways and Mechanisms (University of Utah)

Research Technologist (STEMCELL Technologies Inc.)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Immune Cell Culture (STEMCELL Technologies Inc.)

Chief – Laboratory of Allergic Diseases (National Institute of Allergy and Infectious Diseases)

Postdoctoral Fellow – Cancer Immunology (University of Alabama at Birmingham)

Postdoctoral Position – Interface of Stem Cell Biology and Immunology (Columbia University)

Faculty Position – Tumor Immunology (University of Utah)

Assistant Professor and Postdoctoral Fellows – Immunology (Chinese Academy of Sciences)

Staff Scientist – Lead Immunotherapy Bioinformatician (Fred Hutchinson Cancer Research Center)

Assistant Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Associate or Full Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

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