Cell Therapy News 20.42 December 16, 2019 | |
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TOP STORYTargeting REGNASE-1 Programs Long-Lived Effector T Cells for Cancer Therapy The authors used an in vivo pooled CRISPR-Cas9 mutagenesis screening approach to demonstrate that, by targeting REGNASE-1, CD8+ T cells were reprogrammed to long-lived effector cells with extensive accumulation, better persistence and robust effector function in tumors. REGNASE-1-deficient CD8+ T cells showed markedly improved therapeutic efficacy against mouse models of melanoma and leukemia. [Nature] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Researchers report results from treating two- or five-week-old Abcb4-/- mice with an AAV vector expressing human ABCB4, resulting in significant decreases of PFIC3 disease biomarkers. All male mice achieved a sustained therapeutic effect up through 12 weeks, but the effect was achieved in only 50% of females. [Nat Commun] Full Article Investigators utilized intracerebroventricular transplantation of bone marrow-derived mesenchymal stem cells (MSCs) as a means to enhance hippocampal neurogenesis in the ketamine-induced neurodevelopmental murine model for schizophrenia. Syngeneic MSCs successfully engrafted and survived for up to three months following transplantation. [Mol Psychiatry] Abstract With the BRAVE approach, virus particle displayed a peptide, derived from a protein, of known function on the AAV capsid surface, and a unique molecular barcode in the packaged genome. The sequencing of RNA-expressed barcodes from a single-generation in vivo screen allows the mapping of putative binding sequences from hundreds of proteins simultaneously. [Proc Natl Acad Sci USA] Abstract | Press Release To evaluate the effects of 11R‐p38I110, porcine islets were incubated with 10 µM 11R-p38I110 or a mutant form designated 11R-mp38I110. After islet transplantation, blood glucose levels reached the normoglycemic range in 58.3% and 0% of diabetic mice treated with 11R-p38I110 or 11R-mp38I110, respectively. [Am J Transplant] Abstract Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes Scientists showed that conformally coated stem-cell (SC) islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC derived islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. [Stem Cell Reports] Full Article Researchers developed a novel model of aganglionosis in which enteric neural crest-derived cells express diphtheria toxin (DT) receptor. Local DT injection into the colon wall resulted in focal, specific, and sustained enteric nervous system ablation without altering gastrointestinal transit or colonic contractility, allowing improved survival over other aganglionosis models. [Sci Rep] Full Article Investigators tried to control the amount of murine interferon-γ (IFN-γ) secreted from transplanted murine mesenchymal stem cell line C3H10T1/2 cells to achieve safe cell-based IFN-γ gene therapy for cancer. C3H10T1/2 cells were transfected with HSVtk- and murine IFN-γ-expressing plasmid vectors to obtain C3H10T1/2/HSVtk/IFN-γ cells. C3H10T1/2/HSVtk/IFN-γ cells released IFN-γ and were sensitive to ganciclovir. [Sci Rep] Full Article The vector genome of 5.73 kb was packaged into VP2-depleted adeno-associated virus (AAV) particles, which did not improve cargo capacity. Reprogrammed hepatocytes were treated with AI-SL.AAV2ΔVP2 and subsequently transplanted, resulting large clusters of FAH-positive hepatocytes. [iScience] Abstract | Graphical Abstract Subscribe to one of our other 19 science newsletters such as Mesenchymal Cell News & ESC & iPSC News. | |
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REVIEWSThe Influence of Environment and Origin on Brain Resident Macrophages and Implications for Therapy The authors review the emerging literature and discuss the potential implications of origin on microglial function, with particular focus on existing and future therapies using bone-marrow- or stem-cell-derived cells for the treatment of neurological diseases. [Nat Neurosci] Abstract The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent Phase I/II trials show promising preliminary results in patients with multiple myeloma progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. [Haematologica] Abstract Targeting Innate Sensing in the Tumor Microenvironment to Improve Immunotherapy Investigators review the innate sensing pathways related to cancer initiation/progression and therapies, summarize the recent key findings in innate immune sensing related to conventional therapies, evaluate current combination strategies, and highlight the potential issues of combinational therapies in terms of antitumor efficacy and toxicities. [Cell Mol Immunol] Abstract Visit our reviews page to see a complete list of reviews in the cell therapy research field. | |
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INDUSTRY NEWSGenEdit, Inc. announced that it has entered into a worldwide, exclusive license and collaboration agreement with Editas Medicine, Inc., a genome editing company. [GenEdit, Inc. (Business Wire, Inc.)] Press Release Anixa Biosciences Provides Update on CAR-T Program Anixa Biosciences, Inc. announced an update regarding the CAR-T technology it is developing with its partner, Moffitt Cancer Center. Experimental results reported from the laboratory of Dr. Jose Conejo-Garcia, the inventor of Anixa’s CAR-T technology and the Chair of the Department of Immunology at Moffitt, indicate that the potential efficacy of this technology as a treatment for ovarian cancer could be greatly improved through additional genetic engineering. [Anixa Biosciences, Inc.] Press Release WindMIL Therapeutics announced that the first patient has been dosed in a Phase IIa clinical trial to determine the safety and efficacy of MILs alone and in combination with an anti-PD-1 in patients with locally advanced unresectable or metastatic non-small cell lung cancer who are refractory to or have relapsed on an anti-PD-1-containing regimen. [WindMIL Therapeutics] Press Release Gritstone Oncology, Inc. announced that the company has presented preliminary Phase I GRANITE immunogenicity data demonstrating the rapid, robust and consistent induction of large numbers of CD8+ T cells against multiple neoantigens in four solid tumor patients with available IFN-g ELISpot data within the first two dosing cohorts. [Gritstone Oncology, Inc.] Press Release | |
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POLICY NEWSUK Election Dashes Scientists’ Hopes of Staying in the EU The United Kingdom is now firmly on the path towards leaving the European Union, after the Conservative party won a majority of 79 seats in yesterday’s general election – a result that has major implications for science. [Nature News] Editorial United States Drops Charges against Two More Scientists after Iran Prisoner Swap US authorities have dropped charges against two researchers accused of attempting to export chemicals to Iran in violation of trade sanctions. The decision follows a prisoner swap in which the United States freed a third researcher who was charged alongside them – and imprisoned. [Nature News] Editorial
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REGULATORYFDARegulation Requiring an Approved New Drug Application for Drugs Sterilized by Irradiation (FR Doc. No:2019-27046) Notice MHRAMHRA Guidance and Publications About a Possible No-Deal Brexit Notice
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EVENTSNEW Tuberculosis: Immunity and Immune Evasion Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Scientist – Functional Pharmacology (Genentech, Inc.) Postdoctoral Position – Pancreatic Islet Graft Survival (University of Alberta) Postdoctoral Researcher – Ciliopathies and Neurogenetics (University of Alberta) Postdoctoral Researcher – Wnt Signaling (German Cancer Research Center in the Helmholtz Association) Technical Officer – Micro-Injectionist (European Molecular Biology Laboratory) Junior Research Fellow – Synthetic Biology (Dresden University of Technology) Post-doctoral fellow – Cancer Immunology/Bioengineering (West Virginia University) Postdoctoral Fellow – Cancer Research (BC Cancer) Research Assistant – Cancer Research (BC Cancer) Postdoctoral Fellow – Cancer Therapy (Purdue University) Postdoctoral Fellow – Single Cell Genomics (BC Cancer) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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