Human Immunology News Volume 5.28 | Jul 18 2017

TOP STORY

Promising Results in Trial of Engineered T Cells in High-Risk Leukemia

Participants’ disease-fighting T cells were removed from their blood and genetically engineered in a lab to produce an artificial receptor, called a chimeric antigen receptor (CAR), that empowered them to recognize and destroy cancer cells bearing a target molecule called CD19. Fourteen of 19 experienced a partial or complete regression of their disease in their lymph nodes. [Press release from Fred Hutchinson Cancer Research Center discussing online prepublication in the Journal of Clinical Oncology] Press Release | Full Article | Video | Video

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Continuous Immunotypes Describe Human Immune Variation and Predict Diverse Responses

The authors showed that the same three key combinations of immune cell population frequencies can define an individual’s immunotype and predict a diverse set of functional responses to cytokine stimulation. They found that, even though interindividual variations in specific cell population frequencies could be large, unrelated individuals of younger age have more homogeneous immunotypes than older individuals. [Proc Natl Acad Sci USA] Full Article

SIRPA-Inhibited, Marrow-Derived Macrophages Engorge, Accumulate, and Differentiate in Antibody-Targeted Regression of Solid Tumors

SIRPα on macrophages from mouse and human marrow was inhibited to block recognition of its ligand, the “marker of self” CD47 on all other cells. These macrophages were then systemically injected into mice with fluorescent human tumors that had been antibody targeted. Within days, the tumors regressed, and single-cell fluorescence analyses showed that the more the macrophages engulfed, the more they accumulated within regressing tumors. [Curr Biol] Abstract | Graphical Abstract

Increased IFN-γ⁺ T Cells Are Responsible for the Clinical Responses of Low-Dose DNA Demethylating Agent Decitabine Anti-Tumor Therapy

The influence of low-dose decitabine on T cells was detected both in vitro and in vivo. Low-dose decitabine therapy enhanced the activation and proliferation of human IFN-γ⁺ T cells, promoted Th1 polarization and activity of cytotoxic T cells both in vivo and in vitro, which in turn inhibited cancer progression and augmented the clinical effects of patients. [Clin Cancer Res] Abstract

Dynamic Gene Expression Response to Altered Gravity in Human T Cells

The authors used the Affymetrix GeneChip^® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity. They found that gene expression in human T cells rapidly responded to altered gravity in the time frame of 20 seconds and 5 minutes. [Sci Rep] Full Article

Imatinib and Nilotinib Off-Target Effects on Human NK Cells, Monocytes, and M2 Macrophages

Scientists investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to tyrosine kinase inhibitor (TKI) concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of neuroblastoma cells. [J Immunol] Abstract

Selective Expression of CCR10 and CXCR3 by Circulating Human HSV-Specific CD8 T-Cells

Investigators identified circulating herpes simplex virus type (HSV)-2-specific CD8 T cells using specific fluorescent tetramer reagents and their expression of several candidate skin-homing associated chemokine receptors was measured using flow cytometry. They found that two chemokine receptors, CXCR3 and CCR10, were up-regulated on HSV-specific CD8 T cells in blood. [J Virol] Abstract

Characterization and Expansion of Autologous GMP-Ready Regulatory T Cells for Treg-Based Cell Therapy in Patients with Ulcerative Colitis

Researchers developed a Good Manufacturing Practices (GMP)-conforming protocol for expansion of ulcerative colitis (UC) regulatory T cells (Tregs) as a rational backbone for future studies on Treg therapy in UC. CD25⁺ blood T cells derived from patients with UC were ex vivo expanded in the presence of IL-2, rapamycin, and anti-CD3/anti-CD28 expander beads using a GMP-conform protocol. [Inflamm Bowel Dis] Abstract

Phase I Study of Chimeric Antigen Receptor Modified T Cells in Treating HER2-Positive Advanced Biliary Tract Cancers and Pancreatic Cancers

This Phase I clinical trial evaluated the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancers and pancreatic cancers. Eleven enrolled patients received one to two-cycles of CART-HER2 cell infusion. [Protein Cell] Full Article

Plant-Made Virus-Like Particles Bearing Influenza Hemagglutinin (HA) Recapitulate Early Interactions of Native Influenza Virions with Human Monocytes/Macrophages

Researchers studied early interactions of plant-made virus-like particles (VLPs) bearing either H1 or H5 with a human monocytoid cell line and human monocyte-derived macrophages as model antigen-presenting cells (APC). Using Vibrio cholerae sialidase and lectins that target α2,6- or α2,3-linked sialic acids, they demonstrated that VLPs bind to these APCs in a sialic acid-dependent manner. [Vaccine] Abstract

Preferential Induction of Cross-Group Influenza a Hemagglutinin Stem–Specific Memory B Cells after H7N9 Immunization in Humans

To better understand the elicitation of hemagglutinin (HA) stem–targeted B cells to group 1 and group 2 influenza subtypes, scientists compared the memory B cell response to group 2 H7N9 and group 1 H5N1 vaccines in humans. Upon H7N9 vaccination, almost half of the HA stem–specific response recognized the group 1 and group 2 subtypes, whereas the response to H5N1 was largely group 1–specific. [Sci Immunol] Full Article

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Secreted Tumor Antigens – Immune Biomarkers for Diagnosis and Therapy

Specific antibody probes have been generated by harvesting antibodies directly from antibody secreting cells through in vitro cultures of lymph node cells or B cell immortalization. Further identification and characterization of tumor antigens is likely to have important implications for cancer diagnostic and biomarker discovery, immune profiling, and the development of cancer vaccines and targeted immunotherapies. [Proteomics] Abstract

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OSE Immunotherapeutics Presents Positive Preclinical Results and Human Ex Vivo Data for OSE-127 (Effi-7) to Support Next Clinical Applications in Inflammatory Bowel Diseases

OSE Immunotherapeutics SA presented new data for OSE-127, an antagonist of the interleukin-7 receptor (IL-7R). The communication entitled “IL-7 pathway controls human T cell homing to the gut and culminates in inflammatory bowel disease mucosa” showed efficacy results for OSE-127 in various preclinical acute or chronic colitis models and ex vivo human biopsies. [Press release from OSE Immunotherapeutics SA discussing research presented at the 17^th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS), Chicago] Press Release

Pfizer Announces FDA Accepts Supplemental New Drug Application for XELJANZ^® (Tofacitinib Citrate) for the Treatment of Adult Patients with Moderately to Severely Active Ulcerative Colitis

Pfizer Inc. announced that the supplemental New Drug Application for XELJANZ^®, an investigational oral treatment for adult patients with moderately to severely active ulcerative colitis, has been accepted for filing by the U.S. FDA. [Pfizer Inc.] Press Release

Stand Up To Cancer, St. Baldrick’s Foundation Hail Green Light for CAR T Cell Therapy for Leukemia

Stand Up To Cancer (SU2C) and the St. Baldrick’s Foundation welcomed the tentative approval by a FDA advisory committee of a revolutionary new therapy for a deadly form of leukemia. [St. Baldrick’s Foundation] Press Release

Novartis CAR-T Cell Therapy CTL019 Unanimously (10-0) Recommended for Approval by FDA Advisory Committee to Treat Pediatric, Young Adult R/R B-Cell ALL

Novartis announced that the US FDA Oncologic Drugs Advisory Committee unanimously recommended approval of CTL019, an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of relapsed or refractory pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). [Novartis] Press Release | Editorial

Provention Bio, Inc. Announces Clinical Program Focused on Intercepting and Preventing the Onset of Type 1 Diabetes

Provention Bio, Inc. announced the in-licensing of an enterovirus vaccine platform, which the company is initially developing to reduce the onset of type 1 diabetes by vaccinating at-risk populations against coxsackievirus B infection. [Provention Bio, Inc.] Press Release

Relatively Few NIH Grantees Get Lion’s Share of Agency’s Funding

The rich have been getting richer in the biomedical research enterprise, and the system favors those who are already doing pretty well, according to a new analysis of National Institutes of Health (NIH) grant recipients. [ScienceInsider] Editorial

Two Female Scientists Sue Salk Institute, Alleging Discrimination at ‘Old Boys Club’

Two senior female scientists are suing their employer, the prestigious Salk Institute for Biological Studies, alleging pervasive, long-standing gender discrimination. In the pair of lawsuits, filed in California Superior Court in San Diego, plaintiffs Vicki Lundblad and Katherine Jones seek unspecified compensation for an array of harms. [ScienceInsider] Editorial

To Woo Public, Europe Opens Up on Animal Experiments, but U.S. Less Transparent

A London-based group that supports the use of animals in biomedical science began inviting the public to take an unusual digital tour of laboratories at four U.K. research institutions. At LabAnimalTour.org, users can watch a monkey with a bolt in its skull forage in its cage at a University of Oxford neuroscience lab and a technician check on some of the 8000 mice housed in one room at the Medical Research Council’s Harwell Institute. [ScienceInsider] Editorial

Why a Flat 2018 Budget Could Tie NSF’s Hands

What would a flat budget mean for the National Science Foundation (NSF)? For many agencies, it means maintaining the status quo. And NSF may have trouble doing anything other than that thanks to some pointed instructions from a key legislator. [ScienceInsider] Editorial

NEW AACR-NCI-EORTC International Conference on Molecular Targets & Cancer Therapeutics
November 5-9, 2017
Boston, Massachusetts, United States

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

NEW 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)

Postdoctoral Position in Mucosal Immunology (Columbia University)

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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