Human Immunology News Volume 5.29 | Jul 25 2017

TOP STORY

Penn Study Suggests that Combining CAR T Cells with Existing Immunotherapies May Overcome Resistance in Glioblastomas

Over the past two years, investigators reported results from a human trial in glioblastoma using chimeric antigen receptor (CAR) T cell therapy, through which a patients’ own T cells were engineered to track down and kill cancer cells that express a tumor-specific protein known as EGFRvIII. Their new study includes full results from the first ten patients treated. [Press release from Penn Medicine discussing online prepublication in Science Translational Medicine] Press Release | Full Article

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The Microvascular Niche Instructs T Cells in Large Vessel Vasculitis via the VEGF-Jagged1-Notch Pathway

Researchers found that circulating CD4 T cells in giant cell arteritis patients have left the quiescent state, actively signal through the Notch pathway, and differentiate into TH1 and TH17 effector cells. In an in vivo model of large vessel vasculitis, exogenous vascular endothelial growth factor (VEGF) functioned as an effective amplifier to recruit and activate vasculitogenic T cells. [Sci Transl Med] Abstract

Identification of a Genetic Variation in ERAP1 Aminopeptidase that Prevents Human Cytomegalovirus miR-UL112-5p-Mediated Immunoevasion

Scientists demonstrated that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65_495-503 peptide to specific CTLs. They showed that the rs17481334 G variant, naturally occurring in the ERAP1 3′ UTR, preserves ERAP1 from miR-UL112-5p-mediated degradation. [Cell Rep] Full Article | Graphical Abstract

Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4⁺ T Cells

Researchers identified a subset of memory CD4⁺ T cells that support HIV entry but not viral gene expression. These cells expressed high levels of CD127, the IL-7 receptor, and were believed to be long-lived lymphocytes. In HIV-infected patients, CD127-expressing cells preferentially localized to extrafollicular lymphoid regions with limited viral replication. [Cell Rep] Full Article | Graphical Abstract

Human Intrahepatic CD69 + CD8⁺ T Cells Have a Tissue Resident Memory T Cell Phenotype with Reduced Cytolytic Capacity

Liver and paired blood mononuclear cells from 17 patients were isolated and CD8⁺ T cells were comprehensively analyzed by flow cytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8⁺ T cells expressed CD69, a marker used to identify T_RM, of which a subset co-expressed CD103. CD69 + CD8⁺ T cells expressed low levels of S1PR1 and KLF2 and a large proportion was CXCR6⁺, resembling liver TRM in mice and liver resident NK cells in human. [Sci Rep] Full Article

CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells

Using flow cytometry investigators showed that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of natural killer (NK) cells and Aspergillus fumigatus they used SEM, CLSM and dSTORM techniques, which clearly demonstrated that NK cells directly interact with A. fumigatus via CD56 and that CD56 is reorganized and accumulated at this interaction site time-dependently. [Sci Rep] Full Article

Induction of a Regulatory Phenotype in CD3⁺ CD4⁺ HLA-DR⁺ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

Using an allogeneic mixed lymphocyte culture to induce an antigen-specific immune response, the role of antigen-presenting cells (APCs) for the presence of human leukocyte antigen DR (HLA-DR) on cluster of differentiation 3 (CD3)⁺ CD4⁺ T cells was evaluated. It was demonstrated that APCs were essential for HLA-DR on CD3⁺ CD4⁺ T cells. [Int J Mol Sci] Full Article

Long-Term Follow Up of Human T-Cell Responses to Conserved HIV-1 Regions Elicited by DNA/Simian Adenovirus/MVA Vaccine Regimens

The authors focused T cells on highly conserved regions of the HIV type 1 (HIV-1) proteome and this was achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8⁺ T cells capable of in vitro HIV-1 inhibition. They assessed the durability of these responses. [PLoS One] Full Article

TCR-Ligand Dissociation Rate Is a Robust and Stable Biomarker of CD8⁺ T Cell Potency

Scientists performed a comprehensive study of T cell receptor (TCR)-peptide-major histocompatibility molecules (pMHC) off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8⁺ T cell clones from melanoma patients and healthy donors. They demonstrated that monomeric TCR-pMHC dissociation rates accurately predict the extent of cytotoxicity, cytokine production, polyfunctionality, cell proliferation, activating/inhibitory receptor expression, and in vivo antitumor potency of naturally occurring antigen-specific CD8⁺ T cells. [JCI Insight] Full Article

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The Immune Contexture in Cancer Prognosis and Treatment

The immune contexture, which is determined by the density, composition, functional state and organization of the leukocyte infiltrate of the tumor, can yield information that is relevant to prognosis, prediction of a treatment response and various other pharmacodynamic parameters. Several complementary technologies can be used to explore the immune contexture of tumors, and to derive biomarkers that could enable the adaptation of individual treatment approaches for each patient, as well as monitoring a response to anticancer therapies. [Nat Rev Clin Oncol] Abstract

Human T Cell Immunosenescence and Inflammation in Aging

Researchers examine the role of NF-κB activation and its dysregulation and how NF-κB activity differs among subgroups of T cells. They explore emerging hypotheses about immunosenescence and changes in T cell behavior with age, including consideration of the T cell antigen receptor and regulatory T cells. [J Leukoc Biol] Abstract

Regional Delivery of Chimeric Antigen Receptor (CAR) T-Cells for Cancer Therapy

Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery. The authors reviewed completed clinical trials for the treatment of glioblastoma and metastatic colorectal cancer and examined the data in these studies for safety, efficacy, and potential advantages that regional delivery may confer over systemic delivery. [Cancers] Full Article

Visit our reviews page to see a complete list of reviews in the human immunology research field.

Neon Therapeutics and Apexigen Announce Immuno-Oncology Clinical Trial Collaboration

Neon Therapeutics, Inc. and Apexigen, Inc. announced an immuno-oncology clinical trial collaboration. Under this agreement, the companies plan to evaluate Neon Therapeutics’ proprietary personalized neoantigen vaccine, NEO-PV-01, in combination with Apexigen’s CD40 agonist antibody, APX005M, for the treatment of patients with metastatic melanoma. [Neon Therapeutics, Inc.] Press Release

Lilly and Nektar Therapeutics Announce Alliance to Develop and Commercialize NKTR-358, a Novel Autoimmune Therapy

Eli Lilly and Company and Nektar Therapeutics announced a strategic collaboration to co-develop NKTR-358, a novel immunological therapy discovered by Nektar. NKTR-358, which achieved first human dose in Phase I clinical development in March of 2017, has the potential to treat a number of autoimmune and other chronic inflammatory conditions. [Eli Lilly and Company] Press Release

ABL Awarded NIH Contract for HIV Vaccine Development Worth up to $318 Million

ABL, Inc. announced it has been awarded the recompetition of the contract for Preclinical Development Support by the Division of AIDS within the National Institute of Allergy and Infectious Disease of the National Institutes of Health. The contract will run for a total of seven years with a maximum funding level of $318 million. [ABL, Inc.] Press Release

Cellectis Granted Patent for CRISPR Use in T-Cells

Cellectis announced the grant by the European Patent Office of patent No. EP3004337 for the invention of using RNA-guided endonucleases, such as Cas9 or Cpf1 for the genetic engineering of T-cells. [Cellectis] Press Release

Compugen Announces Issuance of U.S. Patent for COM701, its Lead Immuno-Oncology Product Candidate

Compugen Ltd. announced that the United States Patent and Trademark Office has issued a patent for COM701, the company’s lead immuno-oncology therapeutic antibody candidate. [Compugen Ltd.] Press Release

BiondVax Reports Positive Phase IIb Clinical Trial Results for its Universal Flu Vaccine

BiondVax Pharmaceuticals Ltd. and the UNISEC consortium reported statistically significant positive results from the Phase IIb clinical trial of M-001, BiondVax’s universal flu vaccine candidate. [BiondVax Pharmaceuticals Ltd.] Press Release

Celyad Announces Initiation of the SHRINK Trial

Celyad SA/NV announced the initiation of the Standard Chemotherapy Regimen and Immunotherapy with NKR-2 (SHRINK) trial, a third clinical trial with their lead product candidate CYAD-01 targeting metastatic colorectal patients. [Celyad SA/NV] Press Release

French Funding Agency President Resigns amidst Tensions

Michael Matlosz, president and CEO of the French National Research Agency in Paris, resigned following months of controversy over how the agency handles grant proposal evaluations. [ScienceInsider] Editorial

US Defence Agencies Grapple with Gene Drives

The JASONs, a group of elite scientists that advises the US government on national security, has weighed in on issues ranging from cyber security to renewing America’s nuclear arsenal. But at a meeting in June, the secretive group took stock of a new threat: gene drives, a genetic-engineering technology that can swiftly spread modifications through entire populations and could help vanquish malaria-spreading mosquitoes. [Nature News] Editorial

NEW 2017 National Cancer Research Institute (NCRI) Cancer Conference
November 5-8, 2017
Liverpool, United Kingdom

NEW Stem Cell Society Singapore’s (SCSS) Symposium 2017
November 16-17, 2017
Singapore, Singapore

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Associate – Autoimmune Disease Research (Benaroya Research Institute at Virginia Mason)

NEW Postdoctoral Fellow – B Cells in Autoimmune Diseases (Inserm)

Postdoctoral Fellow – Inflammatory Autoimmune Disease (Vanderbilt University Medical Center)

Postdoctoral Position – Molecular Biology and Immunology (Harvard Medical School)

Postdoctoral Research Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Neuroimmunology (Duke University)

Postdoctoral Fellow – Immunology (Oxford University)

Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Full Professorship – Immunology (The Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

Postdoctoral Research Fellow – Innate Immunity (Fred Hutchinson Cancer Research Center)

Assistant Associate – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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