Cell Therapy News Volume 21.05 | Feb 10 2020

TOP STORY

CRISPR-Engineered T Cells in Patients with Refractory Cancer

Researchers report a first-in-human Phase I clinical trial to test the safety and feasibility of multiplex CRISPR-Cas9 editing to engineer T cells in three patients with refractory cancer. Two genes encoding the endogenous T cell receptor chains, TCRα and TCRβ were deleted in T cells to reduce TCR mispairing and to enhance the expression of a synthetic, cancer-specific TCR transgene. [Science] Full Article | Press Release

(Ranked by impact factor of the journal)

Donor MSCs Release Apoptotic Bodies to Improve Myocardial Infarction via Autophagy Regulation in Recipient Cells

In a myocardial infarction model, scientists found that transplanted mesenchymal stem cells (MSCs) released apoptotic bodies (ABs) to enhance angiogenesis and improve cardiac functional recovery via regulating macroautophagy/autophagy in recipient endothelial cells (ECs). Mechanistically, after local transplantation, MSCs underwent extensive apoptosis in the short term and released ABs, which were engulfed by the recipient ECs. [Autophagy] Abstract

AAV-Mediated TIMP-1 Overexpression in Aortic Tissue Reduces the Severity of Allograft Vasculopathy in Mice

Aortic allografts from DBA/2 mice were incubated with control buffer, AAV-enhanced green fluorescence protein, or tissue inhibitor of metalloproteinases 1-loaded adeno-associated virus (AAV-TIMP-1) and transplanted into the infrarenal aorta of C57BL/6 mice. Cyclosporine A was administered daily. Explantation as well as histomorphometric and immunohistochemical evaluation was performed after 30 days. [J Heart Lung Transplant] Abstract

Repair of Retinal Degeneration following Ex Vivo Minicircle DNA Gene Therapy and Transplantation of Corrected Photoreceptor Progenitors

Photoreceptor precursors with the same chromosomal genetic mutation were treated ex vivo using minicircle DNA, a non-viral technique that does not present the packaging limitations of AAV vectors. Following transplantation, genetically modified cells reconstructed a functional retina and supported vision in blind mice harboring the same founder gene mutation. [Mol Ther] Abstract | Graphical Abstract

Schnurri-3 Regulates BMP9-Induced Osteogenic Differentiation and Angiogenesis of Human Amniotic Mesenchymal Stem Cells through Runx2 and VEGF

In vitro and in vivo experimentation showed that Shn3 notably inhibited BMP9-induced early and late osteogenic differentiation of human amniotic mesenchymal stem cells (hAMSCs), expression of osteogenesis-related factors, and subcutaneous ectopic bone formation from hAMSCs in nude mice. [Cell Death Dis] Full Article

CAR T Cells Redirected to CD44v6 Control Tumor Growth in Lung and Ovary Adenocarcinoma Bearing Mice

The authors generated a bicistronic retroviral vector containing the CD44v6 CAR and the HSV-TK Mut2 suicide gene to enhance the safety of the proposed CAR T cell therapy. CD44v6 transduced CAR T cells were homogeneously positive for ΔLNGFR selection marker, were enriched in T central memory and T memory stem cells and displayed a highly activated phenotype. [Front Immunol] Full Article

Infusion-Related Thrombogenesis by Liver-Derived Mesenchymal Stem Cells Controlled by Anticoagulant Drugs in 11 Patients with Liver-Based Metabolic Disorders

Scientists analyzed the induced thrombogenic risk and the safety of adding anticoagulants during intraportal infusions of liver-derived mesenchymal stem cells in patients with Crigler-Najjar and urea cycle disorders. [Stem Cell Res Ther] Full Article

Human Chorionic Gonadotropin Improves the Proliferation and Regenerative Potential of Bone Marrow Adherent Stem Cells and the Immune Tolerance of Fetal Microchimeric Stem Cells In Vitro

Investigators tested the effect of hCG treatment on bone marrow derived adherent stem cells in vitro, isolated from a parous woman, mother of male sons, in order to evaluate its effect on maternal mesenchymal stem cells and in the same time on fetal microchimeric stem cells. [Stem Cell Rev Rep] Abstract

Platelet-Derived Microparticles Mediate the Intra-Articular Homing of Mesenchymal Stem Cells in Early-Stage Cartilage Lesions

In vivo homing assays revealed that platelet-derived microparticles (PMPs) possessed excellent homing capacity, which researchers transferred, to some extent, to synovium-derived mesenchymal stem cells (SMSCs) by coating the cell surface. They measured the expression of homing-related genes in SMSCs exposed to PMPs and identified several upregulated genes. [Stem Cells Dev] Abstract

Cancer Gene Therapy by NF-κB-Activated Cancer Cell-Specific Expression of CRISPR/Cas9 Targeting Telomeres

NF-κB-activated gene expression consisted of an NF-κB-specific promoter formed by fusing an NF-κB decoy sequence with a minimal promoter, which could be bound by the intracellular over-activated NF-κB and thus activated the expression of downstream effector genes in an NF-κB-specific manner. [Gene Ther] Abstract

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Engineering Adeno-Associated Virus Vectors for Gene Therapy

Current research indicates that the genetic modification of AAV vectors may further facilitate the success of AAV gene therapy. Vector engineering can increase AAV transduction efficiency, vector tropism and the ability of the capsid and transgene to avoid the host immune response, as well as optimize the large-scale production of AAV. [Nat Rev Genet] Abstract

The Properties of Human Schwann Cells: Lessons from In Vitro Culture and Transplantation Studies

The author addresses the special properties of nerve-derived human Schwann cells (hSCs) that have resulted to date from both in vitro studies and in vivo research on cell transplantation in animal models and human subjects. A consensus has yet to emerge about the essential attributes of cultured normal hSCs. [Glia] Abstract

Clinical Development on the Frontier: Gene Therapy for Duchenne Muscular Dystrophy

Based on experience with development of a gene transfer therapy agent for Duchenne muscular dystrophy, investigators discuss ways in which gene therapy for rare disease challenges traditional clinical development paradigms, and recommend a step-wise approach for design and evaluation to support broader applicability of gene therapy. [Expert Opin Biol Ther] Abstract

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Lineage Provides Positive Update on Phase I/IIa Clinical Study of OpRegen^® for the Treatment of Dry Age-Related Macular Degeneration

Lineage Cell Therapeutics, Inc. provided an update from its ongoing Phase I/IIa clinical study of OpRegen^®, the company’s retinal pigment epithelium transplant therapy, for the treatment of dry age-related macular degeneration. Dry AMD is a leading cause of adult blindness in the developed world with no FDA-approved treatment options. [Lineage Cell Therapeutics, Inc.] Press Release

AskBio Initiates Phase I Trial of Gene Therapy for Heart Failure

Asklepios BioPharmaceutical and its subsidiary NanoCor Therapeutics have dosed the first patient in a Phase I clinical trial of gene therapy candidate NAN-101 to treat congestive heart failure. Congestive heart failure is characterized by the inability of the heart to supply the necessary blood and oxygen to the body. [Asklepios BioPharmaceutical Verdict Media Limited] Press Release

Trump’s 2021 Budget Drowns Science Agencies in Red Ink, Again

It’s another sea of red ink for federal research funding programs in President Donald Trump’s latest budget proposal. The 2021 budget request to Congress released February 10^th calls for deep, often double-digit cuts to R&D spending at major science agencies. [ScienceInsider] Editorial

Major Cancer Institute Sued by Its Own Researchers Over ‘Tapering’ Funding

Alleging that a leading cancer funder is slashing their support in an “unethical and reckless” way, six prominent cancer researchers at the University of California, San Diego, have filed a lawsuit to compel it to continue its current level of support. [ScienceInsider] Editorial

NEW 46^th Annual Meeting of)European Society for Blood and Marrow Transplantation (EBMT)
March 22-25, 2020
Madrid, Spain

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NEW Postdoctoral Researcher – Cell Therapies for Cancer (Technical University of Denmark)

Postdoctoral Fellow – Inflammation and Cancer (University Hospital of Erlangen)

Lecturer – Clinical Pharmacology (University of Bristol)

Research Assistant – Organoid Modeling for Stem Cell Therapies (Boston Children’s Hospital)

Research Fellow – Regenerative Medicine (University of Edinburgh)

Postdoctoral Researcher – Drug Delivery (University of Minnesota Twin Cities)

Postdoctoral Researchers – Cell Biology (Medicinal Bioconvergence Research Center)

Postdoctoral Scientist – Functional Pharmacology (Genentech, Inc.)

Postdoctoral Fellow – Cancer Research (BC Cancer)

Research Assistant – Cancer Research (BC Cancer)

Postdoctoral Fellow – Single Cell Genomics (BC Cancer)

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