Cell Therapy News 18.32 September 25, 2017 | |
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TOP STORYInvestigators showed that MEK inhibition adversely affects early onset T-cell effector function. They showed that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo. [Nat Commun] Full Article | |
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PUBLICATIONS(Ranked by impact factor of the journal)Beta Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These beta cells adapted insulin secretion to ambient metabolite status and show normal insulin processing. [Diabetes] Abstract Swine induced pluripotent stem cell-vascular smooth muscle cells (VSMCs) seeded onto biodegradable polyglycolic acid scaffolds readily formed vascular tissues, which were implanted subcutaneously into immunodeficient mice and showed further maturation revealed by expression of the mature VSMC marker, smooth muscle myosin heavy chain. [Biomaterials] Abstract Researchers simultaneously encapsulated rat mesenchymal stem cells (MSCs) and AML12 hepatocytes in volvox spheres and extensively evaluated the effects of various culturing modes on cell functions and fates. The data presented significant reductions in AST and ALT levels after the implantation of volvox spheres encapsulating both MSCs and AML12 hepatocytes in vivo. [Acta Biomater] Abstract | Graphical Abstract Investigators established a miRNA in vivo precipitation method to identify unpredictable miRNAs with definite targets in cells. They found that miR-151-3p inhibited LPS-induced IL-6 production by targeting Stat3. [Cell Mol Immunol] Abstract Scientists investigated the efficacy of endometrial regenerative cells (ERCs) in inducing cardiac allograft tolerance and the function of stromal cell-derived factor-1 (SDF-1) in the ERC-mediated immunoregulation. The results showed that ERC-based therapy induced donor-specific allograft tolerance, and functionally inhibiting SDF-1 resulted in severe allograft rejection. [Stem Cells Transl Med] Full Article The authors report that lymphodepleting chemotherapy by cyclophosphamide (CTX) did not lead to increased availability of the endogenous interleukin-7 (IL-7) in mice. Despite of a paucity of IL-7 in the immune milieu, CTX preconditioning allowed adoptively transferred naïve tumor-specific CD4+ T cells to undergo effector differentiation and regain IL-7 receptor α expression, giving rise to IL-7-responsive polyfunctional CD4+ effector cells. [Sci Rep] Full Article Researchers examined the adoptive transfer of ex vivo expanded human cord blood-derived natural killer (NK) cells into humanized mice reconstituted with autologous human cord blood immune cells. They report that ex vivo expanded NK cells were able to survive and possibly proliferate in vivo in humanized mice without exogenous cytokine administration, but not in control mice that lack human immune cells. [Sci Rep] Full Article siRNA-Mediated RNA Interference in Precision-Cut Tissue Slices Prepared from Mouse Lung and Kidney There is a need for novel experimental models that combine the advantages of in vitro and in vivo models to study the effects of siRNA. The authors investigated whether self-deliverable siRNA can be used in precision-cut lung slices and precision-cut kidney slices to achieve RNAi ex vivo. [AAPS J] Full Article An Engineered Biomarker System to Monitor and Modulate Immune Clearance of Cell Therapies Investigators developed an engineered cell system that secretes a luciferase enzyme to sensitively detect cell transplants independent of their locale by a simple blood test. They specifically studied a unique feature of cell transplant pharmacology—namely, immune clearance—using mesenchymal stromal cells as a proof-of-concept cell therapy. [Cytotherapy] Abstract Primary T Cells for mRNA-Mediated Immunotoxin Delivery The authors investigated the potential of human primary T cells to deliver a secreted immunotoxin through transient mRNA transfection. Protocols for the transient transfection of human embryonic kidney cells as well as activated primary human T cells were established. Transient transfection with mRNA coding for the immunotoxins e23-PE38, VEGF-PE38, and its attenuated variant VEGF-PE38D yielded efficient expression and secretion. [Gene Ther] Abstract | |
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REVIEWSChimeric Antigen Receptor T-Cell Therapy — Assessment and Management of Toxicities Scientists describe the multidisciplinary approach adopted at institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy. [Nat Rev Clin Oncol] Abstract Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke The authors highlight some of the recent advances in the field of extracellular vesicles as a therapeutic means to counter stroke. [Stem Cells Transl Med] Full Article Visit our reviews page to see a complete list of reviews in the cell therapy research field. | |
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SCIENCE NEWSCellular Immunotherapy Presentation – Review of Phase I and II ATIR101™ Data Kiadis Pharma N.V. announced that Professor Denis-Claude Roy, Director Cellular Therapy Laboratory, University of Montreal, gave a presentation entitled ‘Post transplant immunotherapy against leukemia without graft-versus-host disease’. [Press release from Kiadis Pharma N.V. discussing research presented at the 4th Cell and Gene Therapy Conference, Boston] Press Release Two Abstracts Featuring Advaxis’ Lm-Based Candidates Selected for Presentation Advaxis, Inc. announced two abstracts were selected for presentation. Both poster presentations feature Advaxis’ proprietary Listeria monocytogenes (Lm)-based technology. [Press release from Advaxis, Inc. discussing research to be presented at the 32nd Annual Society for Immunotherapy Cancer (SITC) Meeting, National Harbor] Press Release | |
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INDUSTRY NEWSSynpromics Announces Gene Therapy Research Partnership with Solid Biosciences Synpromics Ltd announced a new research partnership with Solid Biosciences, LLC. Under the terms of the agreement, Synpromics will provide Solid Biosciences access to a set of key muscle-selective promoter candidates to be used in the development of new treatment options for Duchenne muscular dystrophy. [Synpromics Ltd (Sciad Communications Ltd.)] Press Release eTheRNA Immunotherapies announced it has been awarded a €1 million industrial R&D Projects Grant by Flanders Innovation & Entrepreneurship. The grant will be used by eTheRNA to further develop and optimize its state-of-the-art production process for generating the mRNA components of its TriMix platform, and for clinical trials of innovative and rationally designed mRNA cancer immunotherapies derived from this platform. [eTheRNA Immunotherapies] Press Release Gene Editing Technology Developer Awarded $500,000 Lemelson-MIT Prize Feng Zhang was announced as the recipient of the 2017 $500,000 Lemelson-MIT Prize, the largest cash prize for invention in the United States. Zhang and his team were first to develop and demonstrate successful methods for using an engineered CRISPR-Cas9 system to edit genomes in living mouse and human cells and have turned CRISPR technology into a practical and shareable collection of tools for robust gene editing and epigenomic manipulation. [Massachusetts Institute of Technology] Press Release Bone Therapeutics announced positive interim efficacy results in the Phase I/IIA delayed-union study of its allogeneic bone cell therapy product ALLOB® in 16 patients. [Bone Therapeutics S.A.] Press Release Autolus Limited announced initiation of both the AMELIA and ALEXANDER Phase I/II studies of its novel, dual-targeting, AUTO3 CAR T-cell therapy. [Autolus Limited] Press Release BioLife Solutions, Inc. announced that Cellular Biomedicine Group (CBMG) has validated BioLife’s proprietary CryoStor freeze media for use in CBMG’s planned US Phase I clinical trial of AlloJoin, an off the shelf allogeneic stem cell therapy for knee osteoarthritis. [BioLife Solutions, Inc. (PR Newswire Association LLC.)] Press Release UCSF First in State to Provide FDA-Approved CAR-T for Pediatric Cancer Patients University of California, San Francisco (UCSF) Benioff Children’s Hospital has been certified as the first medical center in California to provide CAR-T therapy for children and young adults with acute lymphoblastic leukemia who have failed standard treatment. [University of California, San Francisco] Press Release Kiadis Pharma Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for ATIR101™ Kiadis Pharma N.V. announces that FDA has granted ATIR101™, Kiadis Pharma’s lead investigational product for blood cancers, the RMAT designation. [Kiadis Pharma N.V.] Press Release AVROBIO, Inc. Expands Rare Disease Pipeline with Gene Therapy to Treat Pompe Disease AVROBIO, Inc. announced the expansion of its pipeline to Pompe disease. This pre-clinical program becomes AVROBIO’s third gene therapy for lysosomal storage disorders, following on the heels of the company’s Phase I Fabry program and pre-Phase I/II Gaucher program. AVROBIO’s gene therapy for Pompe disease utilizes a proprietary lysosomal targeting sequence to deliver high levels of enzyme to lysosomes. [AVROBIO, Inc.] Press Release | |
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POLICY NEWSWhat Germany’s Election Results Mean for Science As Germany reels from an unexpected surge for the far right in the elections, researchers don’t expect much effect on the country’s generous support for science. But with smaller parties standing to gain political influence, battles over issues such as the regulation of gene-edited organisms and how to cut greenhouse-gas emissions could grow fiercer. [Nature News] Editorial Publishers Go After Networking Site for Illicit Sharing of Journal Papers A major scientific publishing group is taking aim at a social networking site for allowing researchers to illegally post copies of their journal papers. The International Association of Scientific, Technical, and Medical Publishers in Oxford, U.K., and The Hague, the Netherlands, has written to ResearchGate, a networking website for researchers, to express concerns over its article-sharing practices. [ScienceInsider] Editorial United Kingdom Sees Dip in European Research Applications after Brexit Vote The number of researchers applying for Europe-funded Marie Curie fellowships in the United Kingdom has dipped slightly since the country’s vote to leave the European Union, data released to Nature show. But there is no evidence yet of a sharp collapse in interest, which some scientists had feared in the wake of the Brexit referendum. [Nature News] Editorial Craig Venter’s Synthetic Biology Company Hit with Gender Discrimination Suit A former employee of a company co-founded by genomics pioneer J. Craig Venter has filed a lawsuit alleging gender discrimination against the firm’s female employees—and alleging harassment by Venter himself. [ScienceInsider] Editorial BIA & MHRA Publish Report ‘Innovation in Life Sciences in a Changing and Dynamic Environment’ The UK BioIndustry Association (BIA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) brought together experts from across the sector to discuss some hot topics and important developments that are having an impact on the changing and dynamic UK life sciences ecosystem. [Medicines and Healthcare Products Regulatory Agency] Press Release
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REGULATORYFDAFood and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practice; Public Workshop (FR Doc. No:2017-20375) Notice Vaccines and Related Biological Products Advisory Committee; Notice of Meeting (FR Doc. No:2017-20240) Notice
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EVENTSNEW Keystone Symposia: T Cell Dysfunction, Cancer and Infection Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Associate – Infection and Immunity (University College London) Research Technologist – Immunotherapy (STEMCELL Technologies Inc.) Research Scientist – Immuno-Oncology (Kymab Ltd) Technologist – Cell Therapy (Yale New Haven Health) Researcher – Skeletal Tissue Engineering (KU Leuven) Postdoctoral Fellow – Cell Biology, Tumor Immunology and Targeted Therapy (University of Minnesota) Postdoctoral Associate – Enhancer RNA Therapy (Sylvester Comprehensive Cancer Center) Research Fellow – Functional Roles of Stem Cell Derived Extracellular Vesicles (Mayo Clinic) 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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