Volume 3.39 | Oct 6

Human Immunology News 3.39 October 6, 2015
Human Immunology News
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Cell Marker Enables Prognosis about the Course of Infections
For the first time, researchers managed to create a molecular profile of protective cells. By studying these immune cells from patients’ blood, the researchers were able to predict the course of infections. [Press release from Technische Universität München discussing online prepublication in Nature Communications] Press Release | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Efficient Modification of CCR5 in Primary Human Hematopoietic Cells Using a megaTAL Nuclease and AAV Donor Template
Scientists integrated sequences coding chimeric antigen receptors (CARs) into the CCR5 locus, and the resulting targeted CAR T cells exhibited antitumor or anti-HIV activity. [Sci Transl Med] Abstract

miR-142-5p and miR-130a-3p Are Regulated by IL-4 and IL-13 and Control Profibrogenic Macrophage Program
Investigators showed that IL-4 and IL-13 induce miR-142-5p and downregulate miR-130a-3p in macrophages; these changes sustain the profibrogenic effect of macrophages. In vitro, miR-142-5p mimic prolongs STAT6 phosphorylation by targeting its negative regulator, SOCS1. Blocking miR-130a relieves its inhibition of PPARγ, which coordinates STAT6 signaling. [Nat Commun] Full Article

‘Emergency Exit’ of Bone-Marrow-Resident CD34+CD226(DNAM-1)brightCXCR4+-Committed Lymphoid Precursors during Chronic Infection and Inflammation
Flow cytometric analysis of peripheral blood mononuclear cells in chronic inflammatory disorders, both infectious and non-infectious, revealed the presence of a CD34+CD226(DNAM-1)brightCXCR4+ cell population displaying transcriptional signatures typical of common lymphocyte precursors and giving rise to natural killer-cell progenies with high expression of activating receptors and mature function and even to α/β T lymphocytes. [Nat Commun] Full Article

CD56dimCD57+NKG2C+ NK Cell Expansion Is Associated with Reduced Leukemia Relapse after Reduced Intensity HCT
Investigators recently described a specialized subset of human natural killer (NK) cells with a CD56dimCD57+NKG2C+ phenotype that expand specifically in response to cytomegalovirus reactivation in hematopoietic cell transplant (HCT) recipients and exhibit properties characteristic of adaptive immunity. In this study, they hypothesized that these cells mediate relapse protection and improve post-HCT outcomes. [Leukemia] Abstract

Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T Cells
Researchers showed that large numbers of FOXP3+ regulatory T cells (Treg) can be isolated and expanded from a single thymus. Expanded thymic Tregs had stable FOXP3 expression and long telomeres, and suppressed proliferation and cytokine production of activated allogeneic T cells in vitro. [Am J Transplant] Abstract

IL-1β Promotes Th17 Differentiation by Inducing Alternative Splicing of FOXP3
Scientists showed that in human regulatory T (Treg) cells IL-1β promotes excision of FOXP3 exon 7. FOXP3 is not only expressed by Treg cells but is also transiently expressed when naïve T cells differentiate into Th17 cells. [Sci Rep] Full Article

Identification of a FOXP3+CD3+CD56+ Population with Immunosuppressive Function in Cancer Tissues of Human Hepatocellular Carcinoma
In human hepatocellular carcinoma patients, natural T cells were found to be sharply decreased in tumor versus non-tumor tissues. More intriguingly, a substantial fraction of natural T cells assumed FOXP3 expression. [Sci Rep] Full Article

The Regulation of the Treg/Th17 Balance by Mesenchymal Stem Cells in Human Systemic Lupus Erythematosus
Researchers investigated the mechanism of umbilical cord-derived mesenchymal stem cells in the regulation of peripheral regulatory T cells and T helper 17 cells in patients with systemic lupus erythematosus. [Cell Mol Immunol] Abstract

Elevated Circulating CD14lowCD16+ Monocyte Subset in Primary Biliary Cirrhosis Correlates with Liver Injury and Promotes Th1 Polarization
Scientists investigated the phenotype and function of circulating CD16+ monocyte subsets from primary biliary cirrhosis patients. The frequencies of circulating CD14highCD16+ and CD14lowCD16+ subpopulation were increased in disease compared with healthy controls. [Clin Exp Med] Abstract

AAV Capsid CD8+ T-Cell Epitopes Are Highly Conserved across AAV Serotypes
Researchers were able to identify immunodominant major histocompatibility complex class I epitopes for common human leukocyte antigen types by using spleens isolated from subjects undergoing splenectomy for non-malignant indications as a source of large numbers of lymphocytes and restimulating them with single adeno-associated virus (AAV) capsid peptides in vitro. [Mol Ther Methods Clin Dev] Full Article

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Hormonal Control of T-Cell Development in Health and Disease
The authors discuss the accumulating data that shows the thymus gland is under complex and multifaceted hormonal control that affects the process of T-cell development in health and disease. [Nat Rev Endocrinol] Abstract

Antiviral Monoclonal Antibodies: Can They Be More Than Simple Neutralizing Agents?
There is accumulating evidence that monoclonal antibodies (mAbs) can also induce long-lasting protective antiviral immunity by recruiting the endogenous immune system of infected individuals during the period of immunotherapy. Exploiting this property may revolutionize antiviral mAb-based immunotherapies, with benefits for both patients and healthcare systems. [Trends Microbiol] Full Article

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Genentech’s Ocrelizumab First Investigational Medicine to Show Efficacy in People with Primary Progressive Multiple Sclerosis in Large Phase III Study
Genentech announced positive results from a pivotal Phase III study that evaluated the investigational medicine ocrelizumab in people with primary progressive multiple sclerosis. [Press release from Genentech, Inc. discussing research to be presented at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Barcelona] Press Release

Merck Presents Details on Immuno-Oncology Program Including First-in-Man Milestone with Investigational Bi-Functional Immunotherapy
Merck announced that it started investigating a novel, potential first-in-class bi-functional immunotherapy in clinical trials with the potential to offer an alternative therapy to anti-PD-1/anti-PD-L1 and other immunotherapies. [Press release from Merck KGaA discussing research presented at the 2015 European Cancer Congress (ECC), Vienna] Press Release

Aduro Biotech Announces Phase Ib Mesothelioma Trial Featured in Spotlight Poster
Aduro Biotech, Inc. announced the presentation of updated, interim safety and efficacy data from an ongoing Phase Ib clinical trial of its novel immunotherapy, CRS-207, in combination with standard of care chemotherapy in patients with unresectable malignant pleural mesothelioma. [Press release from Aduro Biotech, Inc. discussing research presented at the 2015 European Cancer Congress (ECC), Vienna] Press Release

Caladrius to Present Data Elucidating CLBS20 Mechanism of Action
Caladrius Biosciences, Inc. announced that the company will present new clinical data elucidating the mechanism of action for its lead product candidate, CLBS20. The data suggest correlations between a distinct immune response triggered by CLBS20 and overall survival of melanoma patients. [Press release from Caladrius Biosciences, Inc. discussing research presented to be at the 2015 Stem Cell Meeting on the Mesa (SCMOM), La Jolla] Press Release

Commence Bio to Present at 2015 Stem Cell Meeting on the Mesa
Commence Bio, Inc., a biotechnology company focused on the development of MSC1 and MSC2 cellular immunotherapy platforms for cancer and inflammatory diseases, announced that Thomas Isett, Chief Executive Officer and Co-Founder, will present a corporate overview. [Press release from Commence Bio discussing research to be presented at the 2015 Stem Cell Meeting on the Mesa (SCMOM), La Jolla] Press Release

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Grants Support Baylor Researchers’ Work on Immunotherapy for Leukemia
Two Baylor College of Medicine researchers have received Translational Research Grants from the Leukemia and Lymphoma Society for projects that use immunotherapy approaches to treat leukemia. [Baylor College of Medicine] Press Release

MD Anderson, Theraclone Sciences form OncoResponse
OncoResponse, an immuno-oncology antibody discovery company, has been launched jointly by The University of Texas MD Anderson Cancer Center and Theraclone Sciences. [The University of Texas MD Anderson Cancer Center] Press Release

FDA Approves Game-Changing Immunotherapy Drug to Fight Lung Cancer
The U.S. Food and Drug Administration (FDA) approved the breakthrough drug Keytruda to treat advanced non-small cell lung cancer, signaling a paradigm shift in the way the deadliest of all cancers is treated. [UCLA Jonsson Comprehensive Cancer Center] Press Release

First Human Patient Treated in Phase Ib Study of Advaxis’s ADXS-HER2 in HER2 Expressing Solid Tumor
Advaxis, Inc. announced that the first patient was treated in a Phase Ib dose-escalation clinical study of ADXS-HER2 for the treatment of patients with metastatic HER2 expressing solid tumors. [Advaxis, Inc.] Press Release

Rutgers Cancer Institute of New Jersey Is One of Two National Sites to Offer a New Vaccine Trial for Bladder Cancer
Rutgers Cancer Institute of New Jersey is one of two sites in the nation offering a clinical trial targeting a specific type of bladder cancer with a vaccine treatment. Along with the National Cancer Institute, which is the sponsor of this clinical trial, investigators at the Cancer Institute of New Jersey will look at how effective bacillus Calmette-Guerin is when combined with PANVAC. [Rutgers Cancer Institute of New Jersey] Press Release
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NEW CAR-T Summit 2015
November 12-13, 2015
Boston, United States

NEW 2nd Matrix Biology Ireland (MBI) 2015
December 2-4, 2015
Dublin, Ireland

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NEW Postdoctoral Position – Tumor Immunology (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Position – Cancer Immunology/Immunotherapy (Universität Basel)

NEW Postdoctoral Positions – Immunology (Shanghai Institute of Immunology)

NEW Professor – Immunology (La Jolla Institute for Allergy & Immunology)

Principal Investigator – The Role of Inflammation and the Immune Response in Regenerative Medicine (KU Leuven)

Postdoctoral Researcher – Adverse Immune Signatures and their Prevention in Corneal Transplantation (NUI Galway)

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

Postdoctoral Research Associate – Systems Immunology/Bioinformatics (Benaroya Research Institute at Virginia Mason (BRI))

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))

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