Cell Therapy News 18.39 November 27, 2017 | |
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TOP STORYCyclin D–CDK4 Kinase Destabilizes PD-L1 via Cul3SPOP to Control Cancer Immune Surveillance Scientists report that programmed cell death protein 1 ligand (PD-L1) protein abundance was regulated by cyclin D-CDK4 and the Cullin 3SPOP E3 ligase via proteasome-mediated degradation. Inhibition of CDK4/6 in vivo elevated PD-L1 protein levels, largely by inhibiting cyclin D–CDK4-mediated phosphorylation of SPOP and thereby promoting SPOP degradation by APC/CCdh1. [Nature] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Targeting the T Cell Receptor β-Chain Constant Region for Immunotherapy of T Cell Malignancies Investigators report a new targeting strategy based on the mutually exclusive expression of T cell receptor β-chain constant domains 1 and 2 (TRBC1 and TRBC2). As proof of concept for anti-TRBC immunotherapy, they developed anti-TRBC1 CAR T cells, which recognized and killed normal and malignant TRBC1+, but not TRBC2+, T cells in vitro and in a disseminated mouse model of leukemia. [Nat Med] Abstract | Press Release Granulocyte-Derived TNFα Promotes Vascular and Hematopoietic Regeneration in the Bone Marrow Researchers found that donor hematopoietic cells act on sinusoidal endothelial cells and induce host blood vessel and hematopoietic regeneration after bone marrow (BM) transplantation in mice. Adoptive transfer of BM, but not peripheral, granulocytes prevented the death of mice transplanted with limited numbers of hematopoietic stem cells and accelerated recovery of host vessels and hematopoietic cells. [Nat Med] Abstract The authors found a central role for major histocompatibility complex (MHC) class I in controlling the phagocytic function of macrophages. Disruption of either MHC class I or LILRB1 potentiated phagocytosis of tumor cells both in vitro and in vivo, which defined the MHC class I–LILRB1 signaling axis as an important regulator of the effector function of innate immune cells. [Nat Immunol] Abstract | Press Release TCR Engagement Negatively Affects CD8 but Not CD4 CAR T Cell Expansion and Leukemic Clearance Using an immunocompetent, syngeneic murine model of CD19-targeted CAR T cell therapy for pre–B cell acute lymphoblastic leukemia, in which the CAR is introduced into T cells with known T cell receptor (TCR) specificity, investigators demonstrated loss of CD8 CAR T cell efficacy associated with T cell exhaustion and apoptosis when TCR antigen is present. [Sci Transl Med] Full Article Immunogenic Cell Death Amplified by Co-Localized Adjuvant Delivery for Cancer Immunotherapy Scientists present a new material-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrated their therapeutic potential in murine models of melanoma and colon carcinoma. Dying tumor cells laden with adjuvant nanodepots efficiently promoted activation and antigen cross-presentation by dendritic cells in vitro and elicit robust antigen-specific CD8α+ T-cells in vivo. [Nano Lett] Abstract | Graphical Abstract T Cell-Targeting Nanoparticles Focus Delivery of Immunotherapy to Improve Antitumor Immunity The authors describe antibody-targeted nanoparticles that bind to CD8+ T cells in the blood, lymphoid tissues, and tumors of mice. PD-1+ T cells were successfully targeted in the circulation and tumor. The delivery of an inhibitor of TGFβ signaling to PD-1-expressing cells extended the survival of tumor-bearing mice, whereas free drugs had no effect at such doses. [Nat Commun] Full Article Employing two strategies, scientists generated induced pluripotent stem cell-hepatocyte-like cells (HLCs) and hiHeps from the same donor cell line. Both HLCs displayed partial but markedly improved hepatic function following transplantation in vivo, demonstrating plasticity and the potential for cell-based modeling in the dish and cell-based therapy in the future. [Stem Cell Reports] Full Article | Graphical Abstract Engineering Protein-Secreting Plasma Cells by Homology-Directed Repair in Primary Human B Cells Researchers developed methods for efficient genome editing of primary B cells isolated from peripheral blood. By delivering CRISPR/Cas9 ribonucleoprotein complexes under conditions of rapid B cell expansion, they achieved site-specific gene disruption at multiple loci in primary human B cells. They showed that introduction of B-cell activating factor into plasma cells promotes their engraftment into immunodeficient mice. [Mol Ther] Full Article | Graphical Abstract Using human induced pluripotent stem cells (iPSCs) from two β-thalassemia patients with different HBB gene mutations, the authors devised and tested a universal strategy to achieve targeted insertion of the HBB cDNA in exon 1 of HBB gene using Cas9 and two validated guide RNAs. They observed that HBB protein production was restored in erythrocytes derived from iPSCs of two patients. [Stem Cells Transl Med] Full Article A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection Scientists evaluated the safety and clinical feasibility of umbilical cord-derived mesenchymal stem cell (UC-MSC) therapy in liver transplant patients with acute graft rejection. Four weeks after UC-MSC infusions, alanine aminotransferase levels had decreased markedly and remained lower throughout the 12-week follow-up period. Importantly, allograft histology was improved after administration of UC-MSCs. [Stem Cells Transl Med] Full Article | |
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REVIEWSAdvances, Challenges and Future Directions for Stem Cell Therapy in Amyotrophic Lateral Sclerosis Despite substantial improvements in stem cell technology and promising results in preclinical studies, several questions still remain unanswered, such as the identification of the most suitable and beneficial cell source, cell dose, route of delivery and therapeutic mechanisms. The authors cover publications in this field and comprehensively discuss advances, challenges and future direction regarding the therapeutic potential of stem cells in amyotrophic lateral sclerosis, with a focus on mesenchymal stem cells. [Mol Neurodegener] Full Article Visit our reviews page to see a complete list of reviews in the cell therapy research field. | |
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SCIENCE NEWSResults from 282 Abstracts including Celgene Therapies and Pipeline Compounds to Be Presented Celgene Corporation announced that data from 282 abstracts, including more than 60 oral presentations, evaluating Celgene investigational agents and investigational uses of marketed products will be presented. [Press release from Celgene Corporation discussing research to be presented at the 59th American Society of Hematology Annual Meeting, Atlanta] Press Release | |
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INDUSTRY NEWSNew Deal Could Bring First Treatment for Rare Terminal Disorder in Children Scientists from The University of Manchester believe children suffering from Sanfilippo – a rare terminal disorder that affects children’s brains – could be treated successfully for the first time. [The University of Manchester] Press Release 1 | Press Release 2 LLS Funds $46 Million in New Research to Find Cures The Leukemia & Lymphoma Society® (LLS) committed an additional $46 million to fund the most innovative science at leading medical institutions around the world, including Memorial Sloan Kettering Cancer Center in New York, Dana-Farber Cancer Institute in Boston, City of Hope in Duarte, California, and the Walter & Eliza Hall Institute of Medical Research in Australia. [The Leukemia & Lymphoma Society®] Press Release Sphere Fluidics and Geneva Biotech Receive Eurostars Genome Editing Grant Sphere Fluidics and Geneva Biotech received a €1.6 million grant from Eurostars. The funding will be used to develop large DNA cargo gene delivery and genome engineering systems. [Sphere Fluidics Limited] Press Release Immunotherapy Research for Head and Neck Cancers Gets Boost from V Foundation Grant A team of University of California, San Diego School of Medicine and Moores Cancer Center researchers studying new drugs designed to break resistance to cancer immunotherapy has been awarded a V Foundation for Cancer Research translational grant of $600,000 over three years. [University of California, San Diego] Press Release Cure Brain Cancer Supports Brain Cancer Immunotherapy Trials A three-year fellowship will support Dr. Ryan Cross to translate his research into harnessing immune cells to fight brain cancer, a field known as ‘cancer immunotherapy’. [The Walter and Eliza Hall Institute of Medical Research] Press Release Pluristem Therapeutics Inc. announced that the U.S. Patent and Trademark Office has issued a patent titled, “Skeletal muscle regeneration using mesenchymal system cells.” [Pluristem Therapeutics Inc.] Press Release Eureka Therapeutics, Inc. announced FDA allowance of its investigational new drug application and authorization to commence a Phase I clinical trial for ET190L1-ARTEMISTM T cells in relapsed and refractory CD19+ non-hodgkin lymphoma, including chronic lymphocytic leukemia. [Eureka Therapeutics, Inc.] Press Release Brammer Bio Launches Gene Therapy Product Manufacturing Operations in Massachusetts Brammer Bio announced the completion of renovations and launch of its late-stage clinical capacity and commercial-ready cGMP manufacturing site in Cambridge, Massachusetts for gene therapy products. [Brammer Bio (PR Newswire Association LLC.)] Press Release | |
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POLICY NEWSGene Therapy Hits a Peculiar Roadblock: A Virus Shortage Eager to speed development of revolutionary treatments, the Food and Drug Administration recently announced that it would expedite approval of experimental gene therapies. But the regulatory process may not be the biggest obstacle. [The New York Times] Editorial United Kingdom Relies on Science to Revive Flagging Economy The United Kingdom has laid out how it will pour money into research to boost its economy — including cash for artificial intelligence and other high-tech industries — as the country prepares to leave the European Union in 2019. [Nature News] Editorial Nobel Laureates Demand Release of Iranian Scholar Facing Death Sentence Some 75 Nobel prize winners have called on the Iranian government to release Ahmadreza Djalali, a researcher in disaster medicine who was sentenced to death last month. The letter is the latest and most powerful protest against the ruling by the scientific community so far. [Nature News] Editorial Still No Science Advisor at the White House Ten months into his presidency, Donald Trump has yet to name a science advisor. It’s the longest amount of time a modern president has taken to nominate someone to the position since at least 1976, when Congress established the White House’s Office of Science and Technology Policy. [MIT Technology Review] Editorial
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REGULATORYEMANew Guidelines on Good Manufacturing Practices for Advanced Therapies Notice
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JOB OPPORTUNITIESNEW Postdoctoral Positions – Immunotherapy (University of Houston) Research Technologist – Immunotherapy (STEMCELL Technologies Inc.) Research Scientist – Cellular Immunotherapy (Columbia Center for Translational Immunology) Assistant Scientist – Cancer Therapy Research (University of Miami) Postgraduate Positions – Translational Medicine (Qingdao University) Postdoctoral Position – Cancer Research (Helmholtz Zentrum München) Scientist – Immuno-Oncology (Regeneron Pharmaceuticals, Inc.) Postdoctoral Fellows – ImmunoGenomics (San Raffaele-Telethon Institute for Gene Therapy) Postdoctoral Fellowship – CART-Cell Research (National Institutes of Health) Postdoctoral Fellow – Cardiac Regeneration (Kyoto University) Postdoctoral Fellow – Various Projects (University of Oklahoma) 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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