Human Immunology News Volume 6.15 | Apr 17 2018

TOP STORY

Potent Antitumor Efficacy of Anti-GD2 CAR T Cells in H3-K27M⁺ Diffuse Midline Gliomas

Scientists report that patient-derived mutated histone H3 K27M (H3-K27M)-mutant glioma cell cultures exhibit uniform, high expression of the disialoganglioside GD2. In five independent patient-derived H3-K27M⁺ diffuse midline glioma orthotopic xenograft models, systemic administration of GD2-targeted CAR T cells cleared engrafted tumors except for a small number of residual GD2^lo glioma cells. [Nat Med] Abstract | Press Release

(Ranked by impact factor of the journal)

T Cell Receptor-Regulated TGF-β Type I Receptor Expression Determines T Cell Quiescence and Activation

Investigators showed that active transforming growth factor β (TGF-β) signaling was present in naive T cells, and T cell receptor engagement reduced TGF-β signaling during T cell activation by downregulating TGF-β type 1 receptor through activation of caspase recruitment domain-containing protein 11 and nuclear factor κB. Naive T cells in autoimmune patients exhibited reduced TGF-β type 1 receptor expression and increased T cell receptor-driven proliferation compared to healthy subjects. [Immunity] Abstract | Graphical Abstract

Personalized Cancer Vaccine Effectively Mobilizes Antitumor T Cell Immunity in Ovarian Cancer

The authors conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells pulsed with oxidized autologous whole-tumor cell lysate, which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. [Sci Transl Med] Abstract | Press Release

Patients with CD3G Mutations Reveal a Role for Human CD3γ in T_reg Diversity and Suppressive Function

High throughput sequencing was used to study composition and diversity of the T cell receptor β (TRB) repertoire in regulatory T (T_reg) cells, conventional CD4⁺, and CD8⁺ T cells from six patients with CD3G mutations and healthy controls. T_reg cells of patients with CD3G defects had reduced diversity, increased clonality, and reduced suppressive function. [Blood] Abstract

Modifying Enzymes Are Elicited by ER Stress, Generating Epitopes that Are Selectively Recognized by CD4⁺ T Cells in Patients with Type 1 Diabetes

The authors investigated T cell recognition of peptides that correspond to modified beta cell antigens in subjects with type 1 diabetes. Modified peptides elicited enhanced proliferation by autoreactive T cell clones. [Diabetes] Abstract

Introduction of Genetically-Modified CD3ζ Improves Proliferation and Persistence of Antigen-Specific CTLs

The clinical efficacy of T-cell therapies based on T cells transduced with genes encoding tumor-specific T-cell receptors (TCRs) is related to the in vivo persistence of the T cells. Artificial T cell-activating adapter molecules-transduced TCR-T cells demonstrated improved proliferation and persistence in vitro and in vivo. [Cancer Immunol Res] Abstract | Full Article

Caspase-1 from Human Myeloid Derived Suppressor Cells Can Promote T-Cell Independent Tumor Proliferation

To better define their T cell-independent functions within the tumor, sorted monocytic CD14⁺CD11b⁺HLA-DR^low/- myeloid-derived suppressive cells (mMDSCs) from squamous cell carcinoma patients showed upregulated caspase-1 activity, that was associated with increased IL1 and IL18 expression. In vitro studies demonstrated that mMDSCs promoted caspase-1-dependent proliferation of multiple squamous carcinoma cell lines in both human and murine systems. [Cancer Immunol Res] Abstract | Full Article

Self-Delivering RNA Interference Targeting PD-1 Improves Tumor Specific T Cell Functionality for Adoptive Cell Therapy of Malignant Melanoma

Researchers generated a novel self-delivering siRNA (sdRNA) that knocked down PD-1 expression on healthy donor T cells as well as patient-derived tumor infiltrating lymphocytes (TIL). Their results showed that T cells treated with sdRNA specific for PD-1 had increased IFN-γ secreting capacity and that this modality of gene expression interference could be utilized in their rapid expansion protocol for production of TIL for therapy. [Mol Ther] Abstract | Full Article | Press Release

CD83 Antibody Inhibits Human B Cell Responses to Antigen as well as Dendritic Cell-Mediated CD4 T Cell Responses

As CD83 is expressed on the surface of activated B lymphocytes, scientists hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. They found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. [J Immunol] Abstract

YY1 Upregulates Checkpoint Receptors and Downregulates Type I Cytokines in Exhausted, Chronically Stimulated Human T Cells

T cells infiltrate affected organs in chronic infections and malignancy, but they may fail to eradicate virus-infected cells or tumor because of exhaustion. The authors report a Yin Yang-1 (YY1)-centered mechanism for diverse components that have been correlated with exhaustion. Clinical evaluations confirmed elevated YY1 and enhancer of zeste homolog 2 in melanoma tumor-infiltrating lymphocytes and in PD1⁺ T cells in patients with HIV. [iScience] Full Article

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Current State of Immunotherapy for Glioblastoma

Scientists examine the current state of immunotherapy for gliomas, notably glioblastoma, the implications for combining the current standard-of-care treatment modalities with immunotherapies, potential biomarkers of response, and future directions for glioblastoma immuno-oncology. [Nat Rev Clin Oncol] Abstract

Tumor-Infiltrating B Cells: Their Role and Application in Anti-Tumor Immunity in Lung Cancer

The authors review recent clinical and preclinical studies that outline the role of tumor-infiltrating B lymphocytes in lung cancer development, assess their prognostic significance, and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment. [Cell Mol Immunol] Abstract

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

New Preclinical Studies Reinforce the Potential for Heightened Anti-Cancer Activity of Combination Therapies Based on Immunovaccine’s Proprietary Delivery Platform

Immunovaccine Inc. announced that it presented new research on its T-cell activating platform. [Press release from Immunovaccine Inc. discussing research presented at the 2018 American Association for Cancer Research (AACR) Annual Meeting, Chicago] Press Release

Obsidian Therapeutics Presents Preclinical Data from Regulated Cytokine Programs that Enable CAR-T Therapies with Controllable Functions

Obsidian Therapeutics, Inc. announced the presentation of preclinical data on its regulated cytokine programs. [Press release from Obsidian Therapeutics, Inc. (Business Wire, Inc.) discussing research presented at the 2018 American Association for Cancer Research (AACR) Annual Meeting, Chicago] Press Release

Elios Therapeutics to Present Interim Phase IIb Results of TLPLDC, a Personalized Therapeutic Cancer Vaccine for the Treatment of Melanoma

Elios Therapeutics announced that new interim data from the ongoing Phase IIb clinical trial of the TLPLDC vaccine in patients with stage III and IV, resected melanoma will be presented. [Press release from Elios Therapeutics (PR Newswire Association LLC.) discussing research to be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Bristol-Myers Squibb and Illumina Announce Strategic Collaboration to Develop and Commercialize Companion Diagnostics for Bristol-Myers Squibb’s Oncology Immunotherapies

Bristol-Myers Squibb Company announced a collaboration that will utilize Illumina’s next-generation sequencing technology to develop and globally commercialize in-vitro diagnostic assays in support of Bristol-Myers Squibb’s oncology portfolio. [Bristol-Myers Squibb Company] Press Release

ImmunoCellular Therapeutics Announces Achievement of Next Key Milestone in Stem-to-T-Cell Research Immuno-Oncology Program

ImmunoCellular Therapeutics, Ltd. announced that it has been able to verify successful transfer of the selected T cell receptor genetic material into human hematopoietic stem cells. [ImmunoCellular Therapeutics, Ltd.] Press Release

Baylor University Medical Center Begins Breakthrough CAR-T Cancer Treatment for Patients with Non-Hodgkin’s Lymphoma

Baylor University Medical Center, a part of Baylor Scott & White Health, and Texas Oncology announced that they are now offering CAR-T cancer therapy to treat diffuse large B-cell lymphoma. These providers are working together and are among the first in the nation to treat patients with the only CAR-T cell therapy approved by the FDA to treat this form of cancer. [Baylor Scott and White Health (Newswise, Inc.)] Press Release

City of Hope Certified to Provide First FDA-Approved CAR T Cell Therapy for Pediatric and Young Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia

City of Hope announced that it is a certified treatment center to administer tisagenlecleucel CAR T cell therapy – the first CAR T cell therapy approved by the FDA – to patients up to 25 years of age with B cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse. [City of Hope] Press Release

University Declines to Sanction Doctor Who Referred Patient for Deadly Transplant

The doctor who referred a cancer patient for the first-ever artificial trachea implant will not face disciplinary action from the University of Iceland in Reykjavik, where he works. Patient Andemariam Beyene died after the implant, a polymer scaffold seeded with his own stem cells, failed. [ScienceInsider] Editorial

A Final Dash across the United States: Updates from the 2018 March for Science

The March for Science celebrated its anniversary. And although the turnout around the world was significantly smaller than last year, supporters haven’t lost any of their energy. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Lysosomes and Endocytosis
June 17-22, 2018
Andover, New Hampshire, United States

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

NEW Scientist/Senior Scientist – Lentivirus Production (Obsidian Therapeutics)

NEW Scientist/Senior Scientist – Bioinformatics and Data Sciences (Obsidian Therapeutics)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellowship – Immune Signaling and Metabolism (St. Jude Children’s Research Hospital)

Research Scientist – Biomarker Development (Kymab)

Postdoctoral Position – Onco-ImmunoMetabolism (San Raffaele Scientific Institute)

Assistant/Associate Professor – Immunology (Saint Louis University)

Postdoctoral Fellow – Allergic Disease Inflammation Research (La Jolla Institute for Allergy & Immunology)

Postdoctoral Position – Immune Oncology (H. Lee Moffitt Cancer & Research Institute)

Scientist – Immune Tolerance (Moderna Therapeutics)

Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

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