Human Immunology News Volume 5.43 | Oct 31 2017

TOP STORY

AML-Specific Cytotoxic Antibodies in Patients with Durable Graft versus Leukemia Responses

From B cells of high-risk acute myeloid leukemia (AML) patients with potent and lasting graft versus leukemia responses, the authors isolated monoclonal antibodies directed against antigens expressed on the cell surface of AML cells, but not on normal hematopoietic and non-hematopoietic cells. [Blood] Abstract

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Humanized Mouse Model Supports Development, Function, and Tissue Residency of Human Natural Killer Cells

Scientists describe a human interleukin 15 and human signal regulatory protein alpha knock-in mouse on a Rag2^−/− Il2rg^−/− background (SRG-15). Transplantation of human hematopoietic stem and progenitor cells into SRG-15 mice dramatically improved the development and functional maturation of circulating and tissue-resident human natural killer and CD8⁺ T cells and promoted the development of tissue-resident innate lymphoid cell subsets. [Proc Natl Acad Sci USA] Abstract

Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute Myeloid Leukemia and Its Underlying Mechanisms

Researchers explored the potential of ex vivo expanded healthy donor derived allogeneic CD4 and CD8 double negative cells (DNTs) as a novel cellular immunotherapy for leukemia patients. Expanded DNTs from healthy donors targeted a majority of primary AML cells, including nine chemotherapy-resistant patient samples in vitro, and significantly reduced the leukemia load in patient-derived xenograft models in a DNT-donor unrestricted manner. [Clin Cancer Res] Abstract

CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8⁺ T Cells

Investigators describe a subset of tumor-infiltrating CD8⁺ T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39^highCD8⁺ T cells increased with tumor growth but was absent in lymphoid organs. [Cancer Res] Abstract

T-Cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal Adenocarcinoma

To elucidate mechanisms of immunotherapy resistance, the authors assessed immune parameters in resected human pancreatic ductal adenocarcinoma. They demonstrated significant interpatient variability in T-cell number, localization, and phenotype. [Cancer Immunol Res] Abstract

Vortioxetine Exerts Antiinflammatory and Immunomodulatory Effects on Human Monocytes/Macrophages

A crosstalk between the immune system and depression has been postulated, with a key role played by monocytes/macrophages and cytokines. Investigators examined whether vortioxetine, a multimodal anti-depressive drug, was endowed of antiinflammatory and anti-oxidative activity, leading to immunomodulatory effects on human monocytes and macrophages. [Br J Pharmacol] Abstract

Clinical and Immunologic Evaluation of Three Metastatic Melanoma Patients Treated with Autologous Melanoma-Reactive TCR-Transduced T Cells

Scientists describe preliminary results from a Phase I clinical trial of adoptive cell therapy in which three patients received autologous CD4⁺ and CD8⁺ T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34. This unusual MHC class I-restricted TCR produced functional responses in both CD4⁺ and CD8⁺ T cells. [Cancer Immunol Immunother] Abstract

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

Glycolipid-Peptide Conjugate Vaccines Enhance CD8⁺ T Cell Responses against Human Viral Proteins

Investigators examined the effect of a glycolipid-peptide conjugate vaccine incorporating a natural killer T (NKT) cell-activating glycolipid linked to an MHC class I-restricted peptide from a viral antigen in human peripheral blood mononuclear cells. The vaccine induced CD1d-dependent activation of human NKT cells following enzymatic cleavage, activated human dendritic cells in an NKT-cell dependent manner, and generated a pool of activated antigen-specific CD8⁺ T cells with cytotoxic potential. [Sci Rep] Full Article

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T_H2 Cell Development and Function

Scientists review recent insights into how diverse molecular signals from cellular sources, including dendritic cells, innate lymphoid cells and the epithelium, are integrated by T cells to guide the transcriptional and epigenetic changes necessary for T helper 2 (T_H2) cell differentiation. [Nat Rev Immunol] Abstract

Migrating into the Tumor: A Roadmap for T Cells

Tumors can be divided into ‘hot’ (T cell inflamed) or ‘cold’ (T cell noninflamed) according to the presence of immune cells. The authors discuss variables that influence T cell migration into the tumor microenvironment. [Trends Cancer] Abstract

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

Unum Therapeutics to Present New Data on Its Antibody-Coupled T Cell Receptor (ACTR) Platform

Unum Therapeutics Inc. announced that the company presented on its ACTR platform. The first poster presentation highlighted data from non-clinical studies on effective targeting of HER2-amplified cancers with trastuzumab used in combination with ACTR707, a novel ACTR. [Press release from the Unum Therapeutics Inc. discussing research presented at the 2017 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Philadelphia] Press Release

Apexigen Announces Late-Breaking Oral Presentation for Immune Activating Antibody APX005M

Apexigen, Inc. announced that an abstract for company’s lead I-O agent APX005M, a CD40 agonistic monoclonal antibody, was accepted as a late-breaking oral presentation. [Press release from Apexigen, Inc. discussing research to be presented at the 32^nd Annual Meeting of the Society for Immunotherapy of Cancer (SITC), National Harbor] Press Release

Boehringer Ingelheim Expands Collaboration with Sarah Cannon Research Institute to Investigate Novel Immuno-Oncology Combination Therapy

Boehringer Ingelheim and Sarah Cannon Research Institute announced an expansion of their strategic partnership to bring innovative treatments to cancer patients by developing novel immuno-oncology therapies. [Boehringer Ingelheim] Press Release

Alpine Immune Sciences and Kite Extend Research Term of Collaboration to Create Next-Generation CAR-T and TCRs

Alpine Immune Sciences, Inc. announced it has extended the research term of its worldwide research and license agreement with Kite, a Gilead company. [Alpine Immune Sciences, Inc.] Press Release

Incyte and MacroGenics Announce Global Collaboration and Licensing Agreement for Anti-PD-1 Monoclonal Antibody MGA012

Incyte Corporation and MacroGenics, Inc. announced that the companies have entered into an exclusive global collaboration and license agreement for MacroGenics’ MGA012, an investigational monoclonal antibody that inhibits programmed cell death protein 1 (PD-1). [Incyte Corporation] Press Release

Vedantra Pharmaceuticals Extends Research Collaboration with Neon Therapeutics to Develop Novel Cancer Immunotherapies

Vedantra Pharmaceuticals, Inc. and Neon Therapeutics announced that the companies have extended their non-exclusive research alliance. [Neon Therapeutics] Press Release

Poseida Awarded $19.8 Million CIRM Grant to Support Clinical Trial of P-BCMA-101, a T Stem Cell Memory CAR-T Therapy for Multiple Myeloma

Poseida Therapeutics Inc. announced that the California Institute for Regenerative Medicine (CIRM) awarded a $19.8 million grant to support the clinical development of Poseida’s P-BCMA-101 product candidate. [Poseida Therapeutics Inc.] Press Release

U.S. Oversight of Risky Pathogen Research Has Flaws, Report Finds

The program that keeps watch over the management of dangerous pathogens at research laboratories still isn’t up to snuff, according to a new report from the U.S. Government Accountability Office. [ScienceInsider] Editorial

Six Papers by Disgraced Surgeon Should Be Retracted, Report Concludes

Sweden’s national scientific ethics board, the Expert Group on Misconduct in Research, has concluded that six papers authored by disgraced surgeon Paolo Macchiarini should be retracted. The papers describe the purported clinical success of artificial trachea “seeded” with a patient’s own stem cells. All three patients described in the papers died of complications related to the implant. [ScienceInsider] Editorial

Spanish Government Takes Control of Catalonian Universities

The Spanish government has taken over responsibility for higher education and research in Catalonia, following the region’s unilateral declaration of independence. It will retain control of spending on research centres and universities, which the League of European Research Universities says threatens institutional autonomy. [Nature News] Editorial

NEW Wellcome Genome Campus: Single Cell Biology
March 6-8, 2018
Hinxton, United Kingdom

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