Human Immunology News Volume 4.16 | Apr 26 2016

Lentiviral Hematopoietic Stem Cell Gene Therapy for X-Linked Severe Combined Immunodeficiency
Follow-up data from two older patients demonstrated that lentiviral vector γc transduced autologous hematopoietic stem cell gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at two to three years after treatment. [Sci Transl Med] Abstract | Press Release

CD19 CAR-T Cells of Defined CD4⁺:CD8⁺ Composition in Adult B Cell ALL Patients
Researchers conducted a clinical trial to evaluate CD19 chimeric antigen receptor (CAR)-T cells that were manufactured from defined CD4⁺ and CD8⁺ T cell subsets and administered in a defined CD4⁺:CD8⁺ composition to adults with B cell acute lymphoblastic leukemia (ALL) after lymphodepletion chemotherapy. [J Clin Invest] Full Article | Press Release

Critical Role of CD2 Co-Stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2C-Deficient Humans
Assessment of natural killer (NK) cell repertoires in 60 NKG2C^−/− donors revealed a broad range of NK cell populations displaying characteristic footprints of adaptive NK cells, including a terminally differentiated phenotype, functional reprogramming, and epigenetic remodeling of the interferon-γ promoter. [Cell Rep] Full Article | Graphical Abstract

Immunomodulation by Mesenchymal Stem Cells in Treating Human Autoimmune Disease-Associated Lung Fibrosis
The authors aimed to define the immunopathology involved in pulmonary exacerbation during autoimmunity and to determine the potential of mesenchymal stem cells (MSCs) in correcting these disorders. T cell subsets involved in the process of connective tissue diseases (CTD-IP) were defined, while the regulatory functions of MSCs isolated from the bone marrow of normal individuals on cytotoxic T cells and CTD-UIP human primary lung fibroblasts were investigated in vitro. [Stem Cell Res Ther] Full Article

Characterization of the Immunomodulatory Effects of Meningococcal Opa Proteins on Human Peripheral Blood Mononuclear Cells and CD4⁺ T Cells
Researchers investigated the effects of various Opa⁺ and Opa^– antigens from Neisseria meningitidis strain H44/76 in a range of in vitro conditions using peripheral blood mononuclear cells and purified CD4⁺ T cells, measuring T cell proliferation by CFSE dilution using flow cytometry. [PLoS One] Full Article

TNF Is a Key Cytokine Mediating Neutrophil Cytotoxic Activity in Breast Cancer Patients
Scientists assessed the cytotoxicity of neutrophils from 90 newly diagnosed breast cancer patients, 24 ductal carcinoma in situ patients, 56 metastatic breast cancer patients, and 64 women with no history of cancer. They report that neutrophils from metastatic and newly diagnosed breast cancer patients are significantly more cytotoxic than neutrophils from cancer-free individuals. [npj Breast Cancer] Full Article

PD-1 Marks Dysfunctional Regulatory T Cells in Malignant Gliomas
In both patients with glioblastoma multiforme and healthy subjects, circulating programmed cell death protein 1 (PD-1)^hi Tregs displayed reduced suppression of CD4⁺ effector T cells, production of IFN-γ, and molecular signatures of exhaustion. [JCI Insight] Full Article | Press Release 1 | Press Release 2

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Trained Immunity: A Program of Innate Immune Memory in Health and Disease
The discovery of trained immunity may open the door for novel vaccine approaches, new therapeutic strategies for the treatment of immune deficiency states, and modulation of exaggerated inflammation in autoinflammatory diseases. [Science] Abstract

Toxicity and Management in CAR T-Cell Therapy
Abrogating toxicity has become a critical step in the successful application of chimeric antigen receptor (CAR) T cell technology. To this end, investigators review the reported and theoretical toxicities of CAR T cells and their management. [Mol Ther Oncolytics] Abstract

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First Presentation of Overall Survival Data for Opdivo^® (Nivolumab) Shows Significant Survival Benefit at One-Year versus Investigator’s Choice in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Bristol-Myers Squibb Company announced the first presentation of data from CheckMate -141, a Phase III open-label, randomized trial, evaluating Opdivo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after platinum therapy compared to investigator’s choice of therapy. [Press release from Bristol-Myers Squibb Company discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Late Breaking Data from Advaxis Phase II Study of AXAL Highlights Potential of the Company’s Lm Technology™ Platform
Advaxis, Inc. announced immunological and pathologic data from the company’s ongoing Phase II study of its lead immunotherapy candidate, axalimogene filolisbac (AXAL), in patients with late-stage HPV-associated oropharyngeal cancer. [Press release from Advaxis, Inc. discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Studies Show Continued Promise for Immunotherapy Drugs
Several new immunotherapy drugs are continuing to show benefits across a range of cancer types, according to a slew of new data. The new results confirm their benefit for some melanoma patients, and also suggested they can help certain patients with head and neck cancers, and those with Merkel cell carcinoma. [Press release from Cancer Research UK discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Clinical Data from IIT Using Medigene’s Dendritic Cell (DC) Vaccines in Prostate Cancer Presented
Medigene AG announced that clinical data of a DC vaccine trial for the treatment of prostate cancer were presented. [Press release from Medigene AG discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Immunotherapy Is First to Show Survival Benefit in Head and Neck Cancer
The immunotherapy drug nivolumab has become the first to show a survival benefit in head and neck cancer, after a major international trial found that it was more effective than standard chemotherapy. [Press release from The Institute of Cancer Research discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Biothera Pharmaceuticals Presents New Cancer Immunotherapy Research
Biothera Pharmaceuticals, Inc. announced research providing new insights into the ability of the company’s Phase II cancer immunotherapy to coordinate innate and adaptive immune responses and enhance the effectiveness of combination therapies. [Press release from Biothera Pharmaceuticals, Inc. discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Jounce Therapeutics Presents Data Highlighting Advances from Two Programs in Its Immuno-Oncology Pipeline
Jounce Therapeutics, Inc. presented new preclinical data from two programs in the company’s immuno-oncology pipeline. Jounce’s first presentation highlighted JTX-2011, a humanized ICOS (inducible co-stimulator molecule) agonist antibody being developed for the treatment of solid tumors. [Press release from Jounce Therapeutics, Inc. discussing research presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

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TxCell and Ospedale San Raffaele Launch Collaboration for the Development of CAR-Tregs in Lupus Nephritis
TxCell SA and Ospedale San Raffaele announced they have entered into a strategic R&D collaboration. The collaboration will include a development arm focused on lupus nephritis, as well as a research program dedicated to chimeric-antigen-receptor engineered regulatory T (CAR-Treg) biology. [TxCell SA] Press Release

OncBioMune Enters Joint Venture, Preparation for Phase II Trial of Novel Cancer Vaccine for Prostate Cancer Underway
OncBioMune Pharmaceuticals, Inc. announced the execution of the contract to form a joint venture with Vitel Laboratorios S.A. de C.V. for the purpose of developing and commercializing OncBioMune’s portfolio of innovative cancer therapies in Mexico and Latin America. [OncBioMune Pharmaceuticals, Inc.] Press Release

Bristol-Myers Squibb’s Opdivo^® (Nivolumab) Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for Previously Treated Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Bristol-Myers Squibb Company announced that the U.S. Food and Drug Administration has granted Breakthrough Therapy Designation to Opdivo for the potential indication of recurrent or metastatic squamous cell carcinoma of the head and neck after platinum based therapy. [Bristol-Myers Squibb Company] Press Release

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