Cell Therapy News 18.19 June 5, 2017 | |
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TOP STORYCD7-Edited T Cells Expressing a CD7-Specific CAR for the Therapy of T-Cell Malignancies Investigators demonstrated that targeted genomic disruption of the CD7 gene prevented fratricide and enabled expansion of CD7 CAR T cells without compromising their cytotoxic function. CD7 CAR T cells produced robust cytotoxicity against malignant T cell lines and primary tumors, and were protective in a mouse xenograft model of acute T cell leukemia. [Blood] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists developed a safe vaccine adjuvant for cancer that effectively implements anti-programmed cell death ligand 1 (PD-L1) therapy. Co-administration of ARNAX with a tumor-associated antigen facilitated tumor regression in mouse models, and in combination with anti-PD-L1 antibody, activated tumor-specific cytotoxic T lymphocytes (CTLs) in lymphoid tissues, enhanced CTL infiltration, and overcame anti-PD-1 resistance without cytokinemia. [Cell Rep] Full Article | Graphical Abstract The authors showed that genetic and pharmacologic inactivation of isocitrate dehydrogenase-encoding gene (IDH1) decreased glioblastoma cell growth, promoted a more differentiated tumor cell state, increased apoptosis in response to targeted therapies, and prolonged the survival of animal subjects bearing patient-derived xenografts. [Cell Rep] Full Article | Graphical Abstract A New AAV10-U7-Mediated Gene Therapy Prolongs Survival and Restores Function in an ALS Mouse Model Researchers report an innovative molecular strategy for inducing substantial, widespread, and sustained reduction of mutant human superoxide dismutase (hSOD1) levels throughout the body of SOD1G93A mice, leading to therapeutic effects in animals. Adeno-associated virus serotype rh10 vectors (AAV10) were used to mediate exon-skipping of the hSOD1 pre-mRNA by expression of exon 2-targeted antisense sequences embedded in a modified U7 small-nuclear RNA. [Mol Ther] Abstract Investigators analyzed results of unmanipulated haploidentical allo-stem cell transplantation for adults with acute lymphoblastic leukemia and identified prognostic factors. Forty-four percent of the patients were in first complete remission. One hundred eighty-four (92%) patients achieved engraftment. [J Hematol Oncol] Full Article The authors tested a new approach of stem cell therapy by delivery of induced vascular progenitor cells (iVPCs) grown on polymer micro-bundle scaffolds in a rat model of myocardial infarction. Their in vivo data showed that iVPCs on the micro-bundle scaffold had higher survival, and better retention and engraftment in the myocardium than free iVPCs. [Basic Res Cardiol] Abstract Scientists examined the impact of the intramyocardial administration of bone-marrow-derived, lineage-directed, autologous cardiopoietic mesenchymal stem cells on left ventricular (LV) remodeling in patients with advanced heart failure enrolled in the CHART-1 study. In CHART-1, intramyocardial administration of cardiopoietic stem cells led to reverse remodeling as evidenced by significant progressive decreases in LV end-diastolic volume and end-systolic volume through the 52 weeks of follow-up. [Eur J Heart Fail] Abstract The authors treated DMSXL mice systemically with a 2′-4′-constrained, ethyl-modified (ISIS 486178) antisense oligonucleotide (ASO) targeted to the 3′ UTR of the DMPK gene, which led to a 70% reduction in CUGexp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. [Mol Ther Nucleic Acids] Full Article Investigators recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human telomerase with high avidity, controls human B-cell chronic lymphocytic leukemia progression without severe side-effects in humanized mice. They showed the ability of their approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukemia and B-cell acute lymphoblastic leukemia. [Oncotarget] Full Article Scientists hypothesized that the co-delivery of matrilin-3 with infrapatellar adipose tissue-derived mesenchymal stem cells (Ad-MSCs) may enhance articular cartilage regeneration. The in vivo effect of matrilin-3 co-delivery with Ad-MSCs on cartilage regeneration was assessed in an osteochondral defect model in SD rats: Ad-MSCs and hyaluronic acid were implanted at the defect site with or without matrilin-3. [J Tissue Eng Regen Med] Abstract | |
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REVIEWSEpi-Drugs in Combination with Immunotherapy: A New Avenue to Improve Anticancer Efficacy The authors describe the current strategies to increase immunotherapy responses, the effects of inhibitors of histone deacetylases and inhibitors of DNA methyltransferases on immune modulation, and the advantages of combinatorial therapy over single-drug treatment. [Clin Epigenetics] Full Article Researchers provide an overview of the most recent scientific advances in hematopoietic stem cell-based gene therapy approaches for the treatment of lysosomal storage diseases with particular focus on metachromatic leukodystrophy and mucopolysaccharidosis type I. [J Inherit Metab Dis] Full Article Visit our reviews page to see a complete list of reviews in the cell therapy research field. | |
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SCIENCE NEWSPoseida Therapeutics, Inc. announced preclinical data demonstrating the use of the company’s proprietary high-fidelity genome editing system, NextGEN™ CRISPR, for production of allogeneic “universal donor” chimeric antigen receptor T-cells (CAR-T). [Press release from Poseida Therapeutics, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, Chicago] Press Release CARsgen Presents Phase I Results of CAR-GPC3 T HCC Trial CARsgen Therapeutics disclosed the preliminary safety and efficacy results from a global first-in-man clinical trial of CAR-GPC3 T cell therapy in the treatment for adult patients with relapsed or refractory hepatocellular carcinoma (HCC). Among the 13 patients treated with CAR-GPC3 T cell therapy, all patients well tolerated the study treatment. [Press release from CARsgen Therapeutics (PR Newswire Association LLC.) discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, Chicago] Press Release Kite Pharma, Inc. announced that 73 percent of patients achieved complete remission, including those with incomplete or partial recovery of bone marrow, in an updated analysis of the Phase I ZUMA-3 trial of KTE-C19 in adults with high burden relapsed/refractory acute lymphoblastic leukemia. All responders tested negative for minimal residual disease (MRD). [Press release from Kite Pharma, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, Chicago] Press Release Triple Immunotherapy for Rare Skin Cancer Shows Promise in Small, Early-Stage Trial Three out of four patients treated with an experimental combination of three different therapies for the rare skin cancer known as Merkel cell carcinoma are in complete remission following the treatment, according to study results from a small clinical trial. [Press release from Fred Hutchinson Cancer Research Center discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, Chicago] Press Release | |
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INDUSTRY NEWSACEA Biosciences and Memorial Sloan Kettering Cancer Center have entered into a collaboration to evaluate a personalized ex vivo potency assay using cancer patients’ malignant pleural effusions and ACEA’s xCELLigence Real-Time Cell Analysis instrument to monitor destruction of the cancer cells by the patient’s own genetically modified CAR T cells. [ACEA Biosciences, Inc.] Press Release Inovio Pharmaceuticals, Inc. announced a clinical collaboration with Genentech for advanced bladder cancer. The Phase Ib/II immuno-oncology trial will evaluate Genentech’s atezolizumab in combination with Inovio’s INO-5401, a T cell activating immunotherapy encoding multiple antigens, and INO-9012, an immune activator encoding IL-12. [Inovio Pharmaceuticals, Inc.] Press Release ReNeuron Group plc provided a further update regarding its US clinical and regulatory development strategy for its CTX cell therapy candidate for stroke disability. They received favorable feedback from the FDA at the End of Phase II meeting conducted in April regarding their stroke program. [ReNeuron Group plc] Press Release New Clinical Trial to Study IBD and Graft-versus-Host Disease in Children A new clinical trial at Seattle Children’s Hospital aims to provide doctors with information about how inflammatory bowel disease (IBD) develops in children. The Precision Diagnostics in IBD, Cellular Therapy and Transplantation trial will employ next-generation sequencing and gene expression analyses to better understand how the immune system drives both pediatric IBD and graft-versus-host disease in children with bone marrow transplants. [Seattle Children’s Hospital] Press Release REGENXBIO Inc. announced that the first patient was dosed in a Phase I clinical trial evaluating RGX-314 for patients with wet age-related macular degeneration (wet AMD). This multi-center, open-label, multiple-cohort, dose-escalation clinical trial will assess the safety and tolerability of RGX-314 as a one-time therapy for patients with previously treated wet AMD. [REGENXBIO Inc.] Press Release Voyager Therapeutics Selects Lead Clinical Candidate for Huntington’s Disease Voyager Therapeutics, Inc. announced the selection of VY-HTT01, a clinical candidate for the treatment of Huntington’s disease. VY-HTT01 is composed of an adeno-associated virus capsid and proprietary transgene that harnesses the RNA interference pathway to selectively knock down the production of HTT messenger RNA. [Voyager Therapeutics, Inc.] Press Release Lysogene Completes Enrollment in First International Pivotal Observational Study in MPS IIIA Lysogene announced the completion of enrollment in its Sanfilippo A Multi-national Observational Study. Sanfilippo A is also known as Mucopolysaccharidosis Type IIIA (MPS IIIA). This international multi-center study is to function as a non-concurrent control group for the upcoming Lysogene Phase II/III pivotal gene therapy trial, scheduled to start during the first quarter of 2018. [Lysogene] Press Release Alnylam Pharmaceuticals, Inc. announced that it has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 for the prophylaxis of attacks in patients with acute hepatic porphyria. [Alnylam Pharmaceuticals, Inc.] Press Release | |
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POLICY NEWSNIH Plan to Reduce Overhead Payments Draws Fire President Donald Trump’s administration has brought a long-simmering debate over how the U.S. government supports university research back to a boil. In its 2018 budget proposal, the White House proposes cutting so-called indirect cost payments that the National Institutes of Health (NIH) makes to universities, hospitals, and research institutes by about two-thirds, to 10% of each grant. The administration says the change would allow it to redirect about $4.6 billion now spent each year on overhead—including maintaining labs and complying with regulations—to research. [ScienceInsider] Editorial Trials of Embryonic Stem Cells to Launch in China In the next few months, surgeons in the Chinese city of Zhengzhou will carefully drill through the skulls of people with Parkinson’s disease and inject four million immature neurons derived from human embryonic stem (ES) cells into their brains. Then they will patch the patients up, send them home and wait. This will mark the start of the first clinical trial in China using human ES cells, and the first one worldwide aimed at treating Parkinson’s disease using ES cells from fertilized embryos. [Nature News] Editorial Texas on Track to Become First State to Explicitly Back Stem Cell Therapies Lawmakers in Austin have approved a bill authorizing unapproved stem cell therapies, putting Texas on track to become the first state to explicitly recognize the experimental treatments. [STAT News] Editorial
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REGULATORYFDAVaccines and Related Biological Products Advisory Committee; Notice of Meeting (FR Doc. No:2017-10976) Notice NIHGovernment-Owned Inventions; Availability for Licensing (FR Doc. No:2017-11492) Notice
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EVENTSNEW Gordon Research Conferences: Biomaterials & Tissue Engineering Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Tenure-Track Professorship – Experimental Cell Therapy (University of Bonn) NEW Postdoctoral Position – Tumor Immunology and Cancer Immunotherapy (VIB) Professor – Stem Cell Biology (University College London) Postdoctoral Researcher – Cellular Therapy for Degenerative Disc Disease (NUI Galway) Specialist – Cell Procurement (Celgene Corporation) Head – CAR-T Operations and Technology (Celgene Corporation) Director – Quality Control (KBI Biopharma) Scientist – Analytical Development (KBI Biopharma) PhD Fellow – Experimental Genetic Cardiology (Oslo University Hospital) GMP Manufacturing Director – Cell and Gene Therapy (Fred Hutchinson Cancer Research Center) Research Fellow – Functional Roles of Stem Cell Derived Extracellular Vesicles (Mayo Clinic) Postdoctoral Fellow – Various Projects (University of Oklahoma) GMP Manufacturing Director – Cell and Gene Therapy (Fred Hutchinson Cancer Research Center) Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center) 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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Home Cell Therapy News Volume 18.19 | Jun 5 2017