Immune Regulation News 8.38 October 14, 2016 | |
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TOP STORYTo define the aldesleukin dose response for regulatory T cells (Tregs) and to find doses that increase Tregs physiologically for treatment of type 1 diabetes (T1D), a statistical and systematic approach was taken by analyzing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes, a single centre, non-randomized, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. [PLoS Med] Full Article | |
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PUBLICATIONS(Ranked by impact factor of the journal)The Regulatory Dendritic Cell Marker C1q Is a Potent Inhibitor of Allergic Inflammation Researchers investigated a potential direct role of C1q in downregulating allergic inflammation. In mice with ovalbumin or birch pollen-induced allergic asthma, C1q is as efficacious as dexamethasone to reduce both airway hyperresponsiveness, eosinophil, and ILC2 infiltrates in bronchoalveolar lavages, as well as allergen-specific T helper 2 cells in the lungs. [Mucosal Immunol] Abstract Regulatory T Cells Decrease Invariant Natural Killer T Cell-Mediated Pregnancy Loss in Mice Scientists found that injection of α-galactosylceramide rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual regulatory T cells and their interleukin (IL)-10 and transforming growth factor-β production, and upregulated the levels of interferon-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum. [Mucosal Immunol] Abstract Loss of XIAP Facilitates Switch to TNFα-Induced Necroptosis in Mouse Neutrophils Investigators showed that in response to bacterial lipopolysaccharides (LPS), mouse neutrophils secreted considerable amounts of tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) and, in accordance with earlier reports, X-linked inhibitor of apoptosis (XIAP) prevented LPS-induced hypersecretion of IL-1β also in neutrophils. [Cell Death Dis] Full Article Tiam1/Rac1 Complex Controls Il17a Transcription and Autoimmunity Scientists demonstrated that Tiam1 and Rac1 form a complex with RORγt in the nuclear compartment of Th17 cells, and together bind and activate the Il17 promoter. The clinical relevance of these findings is emphasized by pharmacological targeting of Rac1 that suppresses both murine and human Th17 cells as well as experimental autoimmune encephalomyelitis. [Sci Rep] Full Article Pseudo-Mannosylated DC-SIGN Ligands as Immunomodulants The authors investigated the internalization pattern and the ability of Polyman26 to elicit innate immune responses. Results obtained by confocal microscopy indicate that Polyman26 is internalized by DCs via receptor- mediated endocytosis and is then routed to endolysosomal compartments, thus being presented together with MHC class II molecules, with important implications for the development of vaccines. [Sci Rep] Full Article In vivo, CD25+ regulatory T cell (Treg) depletion shortly after transplantation with splenic cells from G-CSF–treated donors blocks suppression of acute graft-versus-host disease, suggesting Treg involvement in the protection induced by the G-neutrophils. [J Immunol] Abstract Researchers established a collagen-induced arthritis (CIA) model and observed the effect of IL-7Rα antibody in the treatment of CIA mice. They demonstrated that IL-7Rα antibody significantly alleviated clinical symptoms of CIA mice, accompanied with reduced CD4+ T cell number in both spleen and joints. [Mol Immunol] Abstract Microglia, the resident macrophage-like cells in the central nervous system, are important contributors to neuroinflammation and, thus, the authors investigated if type II activated microglia could bias CD4+ T cell responses in a similar manner as type II activated macrophages. [PLoS One] Full Article To investigate the in vivo effect of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA). OVA-specific IgE in sera, OVA-specific T cell response, and the production of cytokines stimulated by the OVA antigen were measured. The transcription level of Foxp3 and the frequency of CD4+CD25+ regulatory T cells were also measured. [Allergol Int] Abstract Subscribe to our sister publications: Human Immunology News & Immunology of Infectious Disease News. | |
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REVIEWSRegulation of T Cell Signaling by Membrane Lipids It has been shown that the modulation of membrane lipids can be used to harness T cell activity to treat cancer and autoimmunity. Therefore, lipid-based immunotherapy might be a promising new clinical strategy. [Nat Rev Immunol] Abstract Immunosuppression for In Vivo Research: State-of-the-Art Protocols and Experimental Approaches The authors summarize current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. They also summarize contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. [Cell Mol Immunol] Full Article Visit our reviews page to see a complete list of reviews in the immune regulation research field. | |
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SCIENCE NEWSBristol-Myers Squibb Company announced results from the CheckMate -275 trial, in which Opdivo had a confirmed objective response rate, the primary endpoint, of 19.6% in platinum-refractory patients with metastatic urothelial carcinoma. [Press release from Bristol-Myers Squibb Company discussing research presented at the 2016 European Society for Medical Oncology (ESMO), Copenhagen] Press Release Leap Therapeutics, Inc. announced the presentation of top-line data from its clinical trial of DKN-01 combination therapy in patients with cholangiocarcinoma. [Press release from Leap Therapeutics, Inc. discussing research presented at the 2016 European Society for Medical Oncology (ESMO), Copenhagen] Press Release Merck announced findings from the final overall survival analysis from the KEYNOTE-002 study investigating the use of KEYTRUDA®, the company’s anti-PD-1 therapy, compared to investigator-choice chemotherapy with a crossover to KEYTRUDA design, in patients with ipilimumab-refractory advanced melanoma. [Press release from Merck discussing research presented at the 2016 European Society for Medical Oncology (ESMO), Copenhagen] Press Release Genentech announced data from the positive, pivotal Phase III OAK study of TECENTRIQ® [Press release from Genentech discussing research presented at the 2016 European Society for Medical Oncology (ESMO), Copenhagen] Press Release Pfizer Inc. announced data from an ongoing, investigational Phase Ib study of INLYTA® combined with the checkpoint inhibitor pembrolizumab, a PD-1 inhibitor known as KEYTRUDA® and marketed by Merck in treatment-naïve patients with advanced renal cell carcinoma. [Press release from Pfizer Inc. (Business Wire, Inc.) discussing research presented at the 2016 European Society for Medical Oncology (ESMO), Copenhagen] Press Release | |
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INDUSTRY NEWSEnGeneIC Ltd. has entered into a research collaboration with, and granted an exclusive licence option to, Takeda Pharmaceutical Company Limited. [EnGeneIC Ltd. (PR Newswire Association LLC.)] Press Release Kymab Limited and EpimAb Biotherapeutics, Inc. announced a cross-licensing and development agreement to develop bispecific therapeutic antibodies against multiple targets. [Kymab Limited] Press Release True North Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for the company’s lead product candidate, TNT009 for the treatment of autoimmune hemolytic anemia, including cold agglutinin disease (CAD), a form of autoimmune hemolytic anemia for which there are limited treatment options available for patients. [True North True North Therapeutics, Inc.] Press Release SELLAS Life Sciences Group reported positive results from the company’s Phase II study of its WT1 first-in-class immunotherapeutic anti-cancer treatment in multiple myeloma patients following autologous stem cell transplantation. [SELLAS Life Sciences Group] Press Release Bristol-Myers Squibb Company announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the approval of Opdivo for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin. [Bristol-Myers Squibb Company] Press Release | |
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POLICY NEWSLeading Scientists Clash over Sweeping UK Research Reforms UK government plans to shake up the way the country’s research is funded are causing dissent among leading British scientists. At the Science Media Centre in London, some of the country’s most eminent researchers clashed over the draft laws, which involve bringing together several existing funding bodies — including the UK’s seven research councils — into one central funder called UK Research and Innovation. [Nature News] Editorial Safety Concerns Blight Promising Cancer Therapy A groundbreaking treatment that arms immune cells called T cells to battle cancer is barreling towards regulators, fueled by unprecedented clinical success and investor exuberance. [Nature News] Editorial A recruitment and retention program launched by the Howard Hughes Medical Institution in Chevy Chase, Maryland, aims to reduce barriers for women and under-represented minorities who seek academic-research careers in the life sciences. [Nature Careers] Editorial The Many Shades of European Postdoc Funding Finding the right grant or fellowship to fund a postdoc can be a challenge, and the situation is all the more complex in Europe, where academic systems, career prospects, and living costs vary widely among countries. [Science Careers] Editorial
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