Human Immunology News Volume 5.44 | Nov 7 2017

TOP STORY

Generation of Higher Affinity T Cell Receptors by Antigen-Driven Differentiation of Progenitor T Cells In Vitro

Scientists describe the in vitro maturation and selection of mouse and human T cells on antigen-expressing feeder cells to develop higher-affinity T cell receptors. The approach takes advantage of natural Tcrb gene rearrangement to generate diversity in the length and composition of CDR3β. [Nat Biotechnol] Abstract

(Ranked by impact factor of the journal)

Hepatitis C Virus-Induced Natural Killer Cell Proliferation Involves Monocyte-Derived Cells and the OX40/OX40L Axis

The authors dissected mechanisms leading to natural killer (NK) cell activation and proliferation in response to hepatitis C virus (HCV). In HCV-containing co-cultures, a higher frequency of NK cells upregulated expression of the high-affinity IL-2 receptor chain CD25, proliferated more rapidly and produced higher amounts of IFN-γ compared to control co-cultures. [J Hepatol] Abstract | Graphical Abstract

Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells Which Target Cytomegalovirus in Glioblastoma

Scientists report prospective results of a pilot trial in which 22 patients with newly-diagnosed glioblastoma were initially enrolled of which 17 patients were randomized to receive cytomegalovirus (CMV) pp65-specific T cells with CMV-dendritic cell vaccination or saline. [Cancer Res] Abstract | Full Article

IL-33 Promotes IL-10 Production in Macrophages: A Role for IL-33 in Macrophage Foam Cell Formation

The authors evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells and the mechanism by which IL-33 upregulates IL-10. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1, but had no effect on CD36 expression. [Exp Mol Med] Full Article

Monomethyl Fumarate Treatment Impairs Maturation of Human Myeloid Dendritic Cells and Their Ability to Activate T Cells

Metabolite monomethyl fumarate treatment induced a less mature phenotype of myeloid dendritic cells (mDCs) with reduced expression of major histocompatibility complex class II, co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB subunits RELA and RELB. mDCs from dimethyl fumarate-treated multiple sclerosis patients also showed the same immature phenotype. [Mult Scler] Full Article

Circulating Exosomes Carrying an Immunosuppressive Cargo Interfere with Cellular Immunotherapy in Acute Myeloid Leukemia

Researchers showed that exosomes isolated from pre-therapy plasma of the acute myeloid leukemia (AML) patients receiving adoptive NK-92 cell therapy block anti-leukemia cytotoxicity of NK-92 cells and other NK-92 cell functions. NK-92 cells did not internalize AML exosomes. [Sci Rep] Full Article

Butyrate and Propionate Inhibit Antigen-Specific CD8⁺ T Cell Activation by Suppressing IL-12 Production by Antigen-Presenting Cells

Given the role of dendritic cells (DCs) in initiating and shaping the adaptive immune response, investigators explored how short chain fatty acids affect the activation of antigen-specific CD8⁺ T cells stimulated with autologous, MART1 peptide-pulsed DC. They showed that butyrate reduces the frequency of peptide-specific CD8⁺ T cells and, together with propionate, inhibit the activity of those cells. [Sci Rep] Full Article

Inhibition of Notch Signaling Has Ability to Alter the Proximal and Distal TCR Signaling Events in Human CD3⁺ αβ T-Cells

Researchers investigated how Notch and T cell receptor (TCR) driven signaling are synchronized in human αβ T cells. Differential expression of Notch receptors, ligands, and target genes was observed on human αβ T cells, which were upregulated on stimulation with α-CD3/CD28 mAb. [Mol Immunol] Abstract

Src-Family Kinases Negatively Regulate NFAT Signaling in Resting Human T Cells

Investigators characterized the role of active Src-family of tyrosine kinases (SFKs) in resting human T cells. Pharmacologic inhibition of active SFKs enhanced distal TCR signaling as measured by IL-2 release and CD25 surface expression following TCR-independent activation. [PLoS One] Full Article

Subscribe to our sister publications: Immunology of Infectious Disease News & Immune Regulation News.

The Trojan Horse – Neuroinflammatory Impact of T Cells in Neurodegenerative Diseases

The authors summarize findings concerning adaptive immune cells in Parkinson’s disease pathogenesis and compare them to Alzheimer’s disease and multiple sclerosis. [Mol Neurodegener] Full Article

Emerging Roles of Innate Lymphoid Cells in Inflammatory Diseases: Clinical Implications

Scientists highlight the role of innate lymphoid cells in human allergic and non-allergic diseases in the airways, gastrointestinal tract and skin, with a focus on new insights into clinical implications, therapeutic options and future research opportunities. [Allergy] Abstract

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

STELARA^® (Ustekinumab) Shows Positive Results in Treatment of Systemic Lupus Erythematosus in Phase II Trial

Janssen Research & Development, LLC announced positive results from a randomized, placebo-controlled Phase II study investigating the anti-IL-12/23 monoclonal antibody STELARA^® in the treatment of active systemic lupus erythematosus. [Press release from Janssen Research & Development, LLC discussing research presented at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting, San Diego] Press Release

Alpine Immune Sciences Presents ALPN-101 Program Data Demonstrating Potent Preclinical Activity in Arthritis and Inflammation

Alpine Immune Sciences, Inc. announced results from preclinical studies evaluating ALPN-101 program dual ICOS/CD28 antagonists generated by the company’s variant immunoglobulin domain platform. [Press release from Alpine Immune Sciences, Inc. discussing research presented at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting, San Diego] Press Release

Kadmon to Present New Data from Ongoing Phase II Study of KD025 in cGVHD

Kadmon Holdings, Inc. announced that it will present updated clinical data from an ongoing Phase II clinical trial evaluating KD025, its Rho-associated coiled-coil kinase 2 inhibitor, in patients with chronic graft-versus-host disease (cGVHD). [Press release from Kadmon Holdings, Inc. discussing research to be presented at the 59^th American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

Syntimmune Announces Clinical Data from First-in-Human Trial of Lead Candidate SYNT001

Syntimmune, Inc. announced robust clinical data from the Phase Ia single ascending dose, double-blind, placebo-controlled trial of Syntimmune’s lead drug candidate, SYNT001. [Press release from Syntimmune, Inc. discussing research to be presented at the 59^th American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

Two Mount Sinai Institutes to Join $215 Million Public-Private Partnership to Increase Patients’ Immunotherapy Success

The Tisch Cancer Institute and the Precision Immunology Institute at Mount Sinai Health System are part of a $215 million public-private Cancer Moonshot research collaboration launched by the National Institutes of Health and eleven leading pharmaceutical companies. [Icahn School of Medicine at Mount Sinai] Press Release

Daiichi Sankyo and Glycotope Announce Option Agreement for Antibody Drug Conjugate Strategic Collaboration and Licensing

Daiichi Sankyo Company, Limited and Glycotope GmbH signed an option agreement for future strategic collaboration and licensing to develop an antibody drug conjugate (ADC) by combining Daiichi Sankyo’s proprietary ADC technology with Glycotope’s investigational tumor-associated TA-MUC1 antibody PankoMab-GEX^®. [Daiichi Sankyo Company, Limited] Press Release

Novartis Submits Application to FDA for Kymriah^™ (Tisagenlecleucel) in Adult Patients with r/r DLBCL, Seeking Second Indication for First-Ever FDA Approved CAR-T Therapy

Novartis announced that the company has submitted a supplemental Biologics License Application to the FDA for Kymriah^™ suspension for intravenous infusion, formerly CTL019, for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. [Novartis AG] Press Release

Concert Pharmaceuticals Announces Completion of Enrollment in First Cohort of CTP-543 Phase IIa Trial

Concert Pharmaceuticals, Inc. announced that it has completed enrollment of the first cohort of its Phase IIa trial evaluating CTP-543. Concert is developing CTP-543 for the treatment of moderate-to-severe alopecia areata, an autoimmune disorder in which the immune system attacks hair follicles, resulting in patchy or complete hair loss. [Concert Pharmaceuticals, Inc.] Press Release

FDA Lifts Clinical Hold on Cellectis Phase I Clinical Trials with UCART123 in AML and BPDCN

Cellectis announced that the FDA has lifted the clinical hold on Phase I trials of Cellectis’ UCART123 product candidate in acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). [Cellectis] Press Release

Court Demands that Search Engines and Internet Service Providers Block Sci-Hub

The American Chemical Society (ACS) has won a lawsuit against Sci-Hub, a website providing illicit free access to millions of paywalled scientific papers. ACS had alleged copyright infringement, trademark counterfeiting and trademark infringement; a district court in Virginia ruled that Sci-Hub should pay the ACS $4.8 million in damages after Sci-Hub representatives failed to attend court. [ScienceInsider] Editorial

Indian Scientists Urged to Speak Out about Pseudoscience

A leading Indian science-advocacy group is urging the country’s researchers to speak out against pseudoscience, which it fears has gained a foothold in the past few years, partly through support from some agencies of the Indian government. [Nature News] Editorial

NEW Keystone Symposia: Myeloid Cells
April 8-12, 2018
Breckenridge, Colorado, United States

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

NEW Postdoctoral Fellow – Mucosal Immunology (University of Lorraine)

Research Technologist – Immunotherapy (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Mucosal Infections (University of Utah)

Postdoctoral Training Fellow – B Cell Immunology (The Francis Crick Institute)

Postdoctoral Positions – Rare Immune Disorders (Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

Tenured Track Faculty – Regenerative and Immune Engineering (Johns Hopkins University Biomedical Engineering)

Scientist – Immune Oncology (Dana-Farber Cancer Institute)

Postdoctoral Researcher – Immunology (University of Luxembourg)

Postdoctoral Fellowship – Tumor Immunology (UT Southwestern Medical Center)

Postdoctoral Fellow – Immunology (University of Rochester Medical Center)

Postdoctoral Researcher – Development of Immune System (Lund University)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Human Immunology News? Click here to submit!

Comments or suggestions? Submit your feedback here.