Cell Therapy News Volume 19.07 | Mar 5 2018

TOP STORY

IL-7 and CCL19 Expression in CAR-T Cells Improves Immune Cell Infiltration and CAR-T Cell Survival in the Tumor

Researchers engineered CAR-T cells to express interleukin (IL)-7 and CCL19 (7 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. [Nat Biotechnol] Abstract

(Ranked by impact factor of the journal)

Restorative Effects of Human Neural Stem Cell Grafts on the Primate Spinal Cord

The authors grafted human spinal cord-derived neural progenitor cells into sites of cervical spinal cord injury in rhesus monkeys. Under three-drug immunosuppression, grafts survived at least nine months postinjury and expressed both neuronal and glial markers. [Nat Med] Abstract | Press Release

Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation

Investigators showed that transplanted somatic and directly induced neural stem cells ameliorate chronic CNS inflammation by reducing succinate levels in the cerebrospinal fluid, thereby decreasing mononuclear phagocyte infiltration and secondary CNS damage. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release

Constitutive and TNFα-Inducible Expression of Chondroitin Sulfate Proteoglycan 4 in Glioblastoma and Neurospheres: Implications for CAR-T Cell Therapy

Chondroitin sulfate proteoglycan 4 (CSPG4).CAR-T cells were effective against glioblastoma-neurospheres with moderate to low expression of CSPG4. This effect was mediated by the in vivo up-regulation of CSPG4 on tumor cells, induced by tumor necrosis factor-α (TNFα) released by the microglia surrounding the tumor. [Sci Transl Med] Abstract

A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing

Scientists report the development of a lipid nanoparticle-mediated delivery system that, with a single administration, enabled significant editing of the mouse transthyretin gene in the liver, with a >97% reduction in serum protein levels that persisted for at least 12 months. [Cell Rep] Full Article | Graphical Abstract | Press Release

Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-Vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo

Researchers showed that human pluripotent stem cell (PSC)-derived kidney organoids, derived in fully defined medium conditions and in the absence of any exogenous vascular endothelial growth factor, developed host-derived vascularization. In vivo imaging of organoids under the kidney capsule confirmed functional glomerular perfusion as well as connection to pre-existing vascular networks in the organoids. [Stem Cell Reports] Full Article | Graphical Abstract | Press Release

Efficient In Vivo Liver-Directed Gene Editing Using CRISPR/Cas9

Scientists report that AAV9-delivery of truncated guide RNAs and Cas9 under the control of a computationally designed hepatocyte-specific promoter lead to liver-specific and sequence-specific targeting in the mouse factor IX gene. [Mol Ther] Abstract

Long Terminal Repeat CRISPR-CAR Coupled ‘Universal’ T Cells Mediate Potent Anti-Leukemic Effects

Investigators describe a self-inactivating lentiviral ‘terminal’ vector platform coupling CAR expression with CRISPR/Cas9 effects through incorporation of an sgRNA element into the ΔU3 3’ long terminal repeat. Robust anti-leukemic effects were demonstrated in humanized immunodeficient mice and were sustained longer than by conventional CAR⁺TCR⁺ T cells. [Mol Ther] Abstract

Integrating HDAd5/35⁺⁺ Vectors as a New Platform for HSC Gene Therapy of Hemoglobinopathies

The authors transduced bone marrow lineage-depleted cells from human CD46-transgenic mice and transplanted them into lethally irradiated recipients. The percentage of γ-globin-positive cells in peripheral blood erythrocytes in primary and secondary transplant recipients was stable and greater than 90%. [Mol Ther Methods Clin Dev] Full Article

Immunologic Targeting of CD30 Eliminates Tumourigenic Human Pluripotent Stem Cells, Allowing Safer Clinical Application of hiPSC-Based Cell Therapy

Transplantation of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) without treatment into NOG mice consistently induced teratoma/tumor formation, with a substantial number of Ki-67-positive cells in the graft at 4 months post-transplant, whereas iPSC-derived CMs treated with brentuximab vedotin prior to the transplantation did not show teratoma/tumor formation, which was associated with absence of Ki-67-positive cells in the graft over the same period. [Sci Rep] Full Article

Concise Review: Is Cardiac Cell Therapy Dead? Embarrassing Trial Outcomes and New Directions for the Future

The authors provide a brief introduction into stem cell therapies for ischemic heart disease. They summarize cell-based and cell-free paradigms, their limitations, and the benefits of using them to target disease. [Stem Cells Transl Med] Full Article

Prospects for Strain-Specific Immunotherapy in Alzheimer’s Disease and Tauopathies

With increasing age, as the incidence of Alzheimer’s disease is increasing, finding a therapeutic intervention is becoming critically important to either prevent or slow down the progression of the disease. Passive immunotherapy has been demonstrated as a successful way of reducing large aggregates and improving cognition in animal models of both tauopathies and Alzheimer’s disease. [npj Vaccines] Full Article

Visit our reviews page to see a complete list of reviews in the cell therapy research field.

Cell and Gene Therapy Catapult Enters into Partnership with the Japanese Society for Regenerative Medicine

The Cell and Gene Therapy Catapult (CGT Catapult) announced it has signed a Memorandum of Understanding with the Japanese Society for Regenerative Medicine (JSRM). This agreement between the CGT Catapult and JSRM aims to advance regenerative medicine and cell and gene therapies in both the UK and Japan. [The Cell and Gene Therapy Catapult] Press Release

ABL Europe Enters into a Collaboration for the GMP Manufacture of Hookipa Biotech’s Heterologous Viral Vector Immunotherapy Platform

Hookipa Biotech AG and ABL Europe SAS have entered in a manufacturing collaboration. Under the agreement, ABL will perform process transfer, scale-up and GMP manufacturing of attenuated replicating viral vectors based on Hookipa’s proprietary arenavirus heterologous TheraT^® platform. [ABL, Inc.] Press Release

Nightstar Therapeutics Announces Initiation of STAR Phase III Registrational Trial for NSR-REP1 in Choroideremia

Nightstar Therapeutics plc announced the initiation of the company’s STAR Phase III registrational trial to study the safety and efficacy of NSR-REP1 in patients with choroideremia. [Nightstar Therapeutics] Press Release

Medigene Receives Approvals for Its First Clinical Trial with TCR Therapy MDG1011

Medigene AG announced that the German Senior Federal Authority “Paul-Ehrlich-Institute” and the relevant ethics committee have approved the study design of the first planned Phase I/II clinical trial with its T cell receptor (TCR)-modified T cell therapy MDG1011. [Medigene AG] Press Release

MeiraGTx Receives EMA PRIME Designation for Achromatopsia Gene Therapy Candidate

MeiraGTx announced the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to MeiraGTx’s gene therapy product candidate A002 for the treatment of patients with achromatopsia due to mutations in the CNGB3 gene. [MeiraGTx Limited] Press Release

Ophthotech Targets Gene Therapy to Expand Its Orphan and Age-Related Retinal Disease Strategy

Ophthotech Corporation announced that the company has initiated an innovative gene therapy research collaboration. As part of Ophthotech’s strategy, the Company has entered into a series of sponsored research agreements with the University of Massachusetts Medical School and its Horae Gene Therapy Center to utilize their “minigene” therapy approach and other novel gene delivery technologies to target retinal diseases. [Ophthotech Corporation] Press Release

California’s Stem Cell Agency Invests in Stem Cell-Based Therapies Targeting Sickle Cell Disease and Cancer

The California Institute for Regenerative Medicine Board awarded $5.74 million to the City of Hope to fund a Phase I clinical trial testing a stem cell-based therapy for adult patients with severe sickle cell disease. [The California Institute for Regenerative Medicine] Press Release

First Longeveron Mesenchymal Stem Cell Treatment Administered to an Infant with Rare Heart Condition as Part of Groundbreaking Clinical Trial

Longeveron announced that its pioneering clinical trial to treat infants with hypoplastic left heart syndrome officially started with the first patient receiving the company’s mesenchymal stem cell therapy in a procedure performed at the University of Maryland Medical Center in Baltimore. [Longeveron (PR Newswire Association LLC.)] Press Release

Sorrento Therapeutics Autologous Anti-CEA CAR-T Cell Therapy for Liver Metastases Demonstrates Therapeutic Activity in Stage IV Pancreas Cancer in a Phase Ib HITM-SURE Trial (NCT02850536)

Sorrento Therapeutics, Inc., TNK Therapeutics, Inc. and Surefire Medical, Inc. announced initial results from the Hepatic ImmunoTherapy for Metastases-Surefire, or HITM-SURE, a Phase Ib single arm trial testing its autologous anti-CEA CAR-T cells administered regionally by hepatic artery infusion via pressure directed microvalve infusion technology in heavily pre-treated patients with refractory CEA-positive liver metastases. [Sorrento Therapeutics, Inc.] Press Release

New NSF Rules on Sexual Harassment Leave Many Questions Unanswered

The National Science Foundation (NSF) in Alexandria, Virginia, hopes that its new policy on sexual harassment will spur universities to deal more aggressively with the pervasive problem. But the additional reporting requirements, which will be officially published in the Federal Register, are far from a definitive statement about how NSF plans to deal with this complex and sensitive subject. [ScienceInsider] Editorial

EU Research Chief’s Next Act: Changing the Future of Academic Publishing

Robert-Jan Smits, one of Europe’s most powerful figures in research, has been appointed as a special envoy on open science at the European Commission, to help push efforts to make all publicly funded research in Europe freely available by 2020. [Science|Business] Editorial

Indian Scientist’s Sacking Spotlights Sexual Harassment

Female scientists in India hope that more academics will report sexual harassment without fear of jeopardizing their career or reputation, after a prominent biologist was sacked for allegedly harassing a staff member. [Nature News] Editorial

Here’s How the Scientists Running for Office Are Doing

They’re trained problem-solvers, but they have to learn to move beyond data to run successful campaigns. [The Atlantic] Editorial

Canadian Science Wins Billions in New Budget

Canadian Prime Minister Justin Trudeau’s administration released its 2018 budget and scientists couldn’t be happier. It includes almost CAD 4 billion (USD 3.1 billion) in new funding for science over the next five years, a significant portion of which will go to the country’s three granting councils. [Nature News] Editorial

TGA

Australian Regulatory Guidelines for Biologicals (ARGB) Notice

NEW IABS: 4^th Cell Therapy Conference Manufacturing and Testing of Pluripotent Stem Cells
June 5-6, 2018
Los Angeles, California, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Fellow – Hematopoiesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Immunology, Immunotherapy, Gene Therapy (City of Hope)

Postdoctoral Fellowship – Functional Genomics of Human Hematopoiesis (Boston Children’s Hospital)

Postdoctoral Researcher – Molecular Cardiology (National Centre for Cardiovascular Research)

Postdoctoral Fellow – Cancer Research (Indiana University School of Medicine)

Postdoctoral Associate – Cardiovascular Science (Duke University)

Postdoctoral Position – Pancreas Development and Stem Cells (Helmholtz Zentrum München)

Postdoctoral Fellowships – Cancer Research (University of Miami)

Tenure-Track Group Leader Position – Pancreatic Cancer Biology (University of Copenhagen)

Professor and Faculty Positions – Various Projects (Academy of Medical Sciences, Zhengzhou University)

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