Human Immunology News Volume 6.05 | Feb 6 2018

TOP STORY

CAR T-Cell Therapy Safe and Effective in Children and Young Adults with Leukemia

Results of the global, multicenter, pivotal Phase II study that led to the first FDA approval of a gene therapy/cell therapy approach known as CAR T-cell therapy. The therapy, tisagenlecleucel, uses a patient’s own white blood cells that have been genetically re-engineered to specifically target and kill cancer cells. [Press release from the Children’s Hospital Los Angeles discussing online prepublication in The New England Journal of Medicine] Press Release | Abstract

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Long-Term Follow-Up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia

The authors conducted a Phase I trial involving adults with relapsed B-cell acute lymphoblastic leukemia who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center. Patients with a low disease burden before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months and a median overall survival of 20.1 months. [N Engl J Med] Abstract | Press Release

In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B-Cell Leukemia

Scientists interrogated and compared the impact of different costimulatory signal domains on CAR-T cells in vivo. Patients with B-cell leukemia were infused with a mixture of two types of CD19-specific CAR-T cells, individually bearing CD28 and 4-1BB costimulatory signaling domains. [Mol Ther] Abstract

Profiling the Pattern of the Human T-Cell Receptor γδ Complementary Determinant Region 3 Repertoire in Patients with Lung Carcinoma via High-Throughput Sequencing Analysis

Researchers characterized the pattern of the human T-cell receptor γδ complementary determinant region 3 (CDR3) repertoire in patients with lung carcinoma (LC) via high-throughput sequencing. The results showed that the diversity of CDR3δ was significantly reduced, and that of CDR3γ was unchanged in LC patients compared with healthy individuals; in addition, LC patients shared significantly more CDR3δ sequences with each other than healthy individuals. [Cell Mol Immunol] Abstract

Differentiation of MSCs from Human iPSCs Results in Downregulation of c-Myc & DNA Replication Pathways with Immunomodulation toward CD4 & CD8 Cells

Using mesenchymal stem cells (MSCs) differentiated from induced pluripotent stem cells (iPSCs) reprogrammed using diverse cell types and protocols, and in comparison to human embryonic stem cell-MSCs and bone marrow-MSCs, investigators performed transcriptome analyses and assessed for functional immunomodulatory properties. Differentiation of MSCs from iPSCs results in decreased c-Myc expression and its downstream pathway along with a concomitant downregulation in the DNA replication pathway. [Stem Cells] Abstract

Il-7 Treatment Supports CD8⁺ MAIT Cell Restoration in HIV-1 Infected Patients on ART

The authors evaluated IL-7 treatment to restore mucosa-associated invariant T (MAIT) cells in peripheral blood of chronically HIV-1 infected individuals on ART. IL-7 led to increased relative and absolute levels of MAIT cells and this expansion occurred primarily in the CD8⁺ subset. [AIDS] Abstract

TGF-β/Smad Signaling Pathway Positively Up-Regulates the Differentiation of Interleukin-9-Producing CD4⁺ T Cells in Human Echinococcus granulosus Infection

Scientists investigated the role of TGF-β/Smad pathway in the regulation of Th9 cells in cystic echinococcosis (CE) patients. The levels of TGF-β, p-Samd3, PU.1 and IL-9 were elevated in the liver of CE patients. [J Infect] Abstract

Axl and Mertk Receptor Tyrosine Kinases Maintain Human Macrophage Efferocytic Capacity in the Presence of Viral Triggers

Investigators showed that whereas pro-inflammatory stimuli consistently downregulated MerTK expression in human monocyte-derived macrophages, stimuli indicative of a viral infection, interferon-α and the TLR3 ligand poly(I:C), specifically induced Axl expression and promoted binding of the bridging molecule Gas6. [Eur J Immunol] Abstract | Full Article

Islet-Reactive CD8⁺ T Cell Frequencies in the Pancreas, but Not in Blood, Distinguish Type 1 Diabetic Patients from Healthy Donors

Scientists showed that clonal ZnT8_186–194-reactive CD8⁺ T cells express private T cell receptors and display equivalent functional properties in type 1 diabetes (T1D) and healthy individuals. Ex vivo analyses further revealed that CD8⁺ T cells reactive to ZnT8_186–194 and other islet epitopes circulate at similar frequencies and exhibit a predominantly naïve phenotype in age-matched T1D and healthy donors. [Sci Immunol] Full Article

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Functions of NKG2D in CD8⁺ T Cells: An Opportunity for Immunotherapy

The authors focus on the similarities and differences between natural killer group 2 member D (NKG2D) and CD28; less well-described characteristics of NKG2D, such as the potential role of NKG2D in CD8⁺ T-cell memory formation, cancer immunity and autoimmunity; and the opportunities for targeting NKG2D in immunotherapy. [Cell Mol Immunol] Abstract

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CAR T-Cell Immunotherapy Named Advance of the Year in Annual ASCO Report

A new and unique new way to treat cancer – CAR T-cell therapy – is poised to transform the outlook for children and adults with certain otherwise incurable cancers. The American Society of Clinical Oncology (ASCO) named this type of adoptive cell immunotherapy the Advance of the Year in its annual report. [American Society of Clinical Oncology] Press Release

Tessa Therapeutics Announces Opening of Recruitment Sites Across the United States for Its Phase III Nose Cancer Immunotherapy Trial

Tessa Therapeutics announced that the Stanford Cancer Institute recently joined the company’s trial network which now consists of seven hospitals across the United States. The company’s Phase III trial targets advanced nose cancer, or nasopharyngeal cancer, with T cell immunotherapy. [Tessa Therapeutics Pte Ltd.] Press Release

The BBVA Foundation Award Goes to James Allison, Creator of the First Immunotherapy to Prove Highly Effective against Cancer

Allison was the first to demonstrate that immunotherapy can treat cancer effectively, initiating an approach that “has provided clinical benefit to many cancer patients” and “stimulated the development of a new class of drugs employing the immune system to fight cancer.” [Banco Bilbao Vizcaya Argentaria, S.A. (PR Newswire Association LLC.)] Press Release

SAB Capra Awarded $225k from NIH

SAB Capra, LLC has been awarded a $225,000 grant from the National Institutes of Health (NIH) to advance its novel immunotherapy platform targeting pandemic influenza in collaboration with Utah State University. [SAB Capra, LLC] Press Release

Health Officials Push for Vaccine against Neglected Tropical Virus

Advocates seek ways to hasten the development of a chikungunya vaccine. [Nature News] Editorial

Japanese Researchers Say Science-Budget Hike Isn’t Enough

Japan will sharply increase funding for science and technology in 2018 after years of stagnant support for the sector. But some scientists and policy experts worry the boost is too little to make up for more than a decade of lackluster science funding. [Nature News] Editorial

Kid Co-Authors in South Korea Spur Government Probe

The South Korean government is expanding an investigation into researchers who named their children as co-authors on papers. The extended probe comes after a government report identified 82 academic papers on which authors had named their children or relatives — many of them in middle or high school — as co-authors on the publications. [Nature News] Editorial

Nature Journals Tighten Rules on Non-Financial Conflicts

What makes a conflict of interest in science? Definitions differ, but broadly agree on one thing: an influence that can cloud a researcher’s objectivity. For some people, that influence can be money. But there are other influences that can interfere, such as institutional loyalty, personal beliefs and ambition. [Nature News] Editorial

NEW International Conference on Lymphocyte Engineering
September 13-15, 2018
Madrid, Spain

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

NEW Senior Director – Immuno-Oncology Research (Alector LLC)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Research Scientist – Oncology Research (MedImmune)

Postdoctoral Researcher – Cellular and Molecular Immunology (Karolinska Institutet)

Postdoctoral Fellow – Immunology/Vascular/Stromal Biology (Hospital for Special Surgery and Weill Cornell Medicine)

Postdoctoral Position – Microbiology and Immunology (University of Maryland)

Head of Laboratory – Cancer Vaccines/Oncolytic Viruses (Boehringer Ingelheim)

Investigator – Immuno-Oncology (Bristol-Myers Squibb)

Scientist – Immuno-Oncology (Bristol-Myers Squibb)

Postdoctoral Fellow – Immune Surveillance (University of Massachusetts)

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