Cell Therapy News Volume 21.00 | Jan 6 2020

TOP STORY

An RNA Vaccine Drives Expansion and Efficacy of Claudin-CAR-T Cells against Solid Tumors

Investigators introduced the developmentally regulated tight junction protein claudin 6 as a CAR target in solid tumors, and a strategy to overcome inefficient CAR-T cell stimulation in vivo. They demonstrated that a nanoparticulate RNA vaccine, designed for body-wide delivery of the CAR antigen into lymphoid compartments, stimulated adoptively transferred CAR-T cells. [Science] Abstract

(Ranked by impact factor of the journal)

Spinal Subpial Delivery of AAV9 Enables Widespread Gene Silencing and Blocks Motoneuron Degeneration in ALS

Researchers showed in adult animals successfully delivered adeno-associated virus throughout the cervical, thoracic and lumbar spinal cord, as well as brain motor centers. One-time injection at cervical and lumbar levels just before disease onset in mice expressing a familial amyotrophic lateral sclerosis (ALS)-causing mutant SOD1 produced long-term suppression of motoneuron disease, including near-complete preservation of spinal α-motoneurons and muscle innervation. [Nat Med] Abstract

Axicabtagene Ciloleucel CD19 CAR-T Cell Therapy Results in High Rates of Systemic and Neurologic Remissions in Ten Patients with Refractory Large B Cell Lymphoma Including Two with HIV and Viral Hepatitis

The authors treated ten patients with DLBCL post-FDA approval in an inner-city tertiary center in the Bronx. Eight patients had received ≥3 lines of therapy, six patients had received prior radiation, and seven had recurrent disease after prior autologous hematopoietic stem cell transplant. The cohort included one patient with HIV, two patients with hepatitis B, and two patients with CNS involvement of lymphoma. [J Hematol Oncol] Full Article

Oligodendrocyte Precursor Cells Transplantation Protects Blood–Brain Barrier in a Mouse Model of Brain Ischemia via Wnt/β-Catenin Signaling

Adult male ICR mice underwent 90 minute transient middle cerebral artery occlusion. After ischemic assault, these mice received stereotactic injection of oligodendrocyte precursor cells. [Cell Death Dis] Full Article

Intralingual and Intrapleural AAV Gene Therapy Prolongs Survival in a SOD1 ALS Mouse Model

Researchers attempted to enhance breathing and prolong survival by suppressing SOD1 expression in respiratory motor neurons using adeno-associated virus expressing an artificial microRNA targeting the SOD1 gene. AAV-miRSOD1 was injected in the tongue and intrapleural space of SOD1^G93A mice and repetitive respiratory and behavioral measurements were performed until end stage. [Mol Ther Nucleic Acids] Abstract | Full Article

7T MRI Predicts Amelioration of Neurodegeneration in the Brain after AAV Gene Therapy

Long-term follow up of GM1 cats treated by bilateral thalamic and deep cerebellar nuclei injection of AAV mediated gene therapy had increased lifespan to eight years of age, compared to an untreated lifespan of ~eight months. Due to risks associated with cerebellar injection in humans, the lateral ventricle was tested as a replacement route to deliver an AAVrh8 vector expressing feline β-galactosidase, the defective enzyme in GM1 gangliosidosis. [Mol Ther Nucleic Acids] Abstract | Full Article

Enhancing the Efficacy of Stem Cell Therapy with Glycosaminoglycans

The authors showed that an FGF2-binding HS variant (HS8) accelerated the expansion of freshly isolated bone marrow human mesenchymal stem cells (hMSCs) without compromising their naivety. Importantly, the repair of osteochondral defects in both rats and pigs was improved after treatment with HS8-supplemented hMSCs when assessed histologically, biomechanically, or by MRI. [Stem Cell Reports] Full Article

Engineering of Functional Cardiac Tubes by Stepwise Transplantation of Cardiac Cell Sheets onto Intestinal Mesentery

Investigators engineered implantable, thick cardiac tubes by the stepwise transplantation of cardiac cell sheets onto intestinal mesentery and confirmed that these cardiac tubes exhibited pulsatile activity and generated an internal pressure. Cell sheets were created by culturing neonatal rat cardiac cells on temperature-responsive dishes. [Heart Vessels] Abstract

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NK Cells for Cancer Immunotherapy

Although tumors may develop several mechanisms to resist attacks from endogenous natural killer (NK) cells, ex vivo activation, expansion and genetic modification of NK cells can greatly increase their antitumor activity and equip them to overcome resistance. Some of these methods have been translated into clinical-grade platforms and support clinical trials of NK cell infusions in patients with hematological malignancies or solid tumors, which have yielded encouraging results so far. [Nat Rev Drug Discov] Abstract

The Future of Stem Cell Therapies for Parkinson Disease

In this review, the authors critically assess the potential trajectory of cell replacement translational and clinical research and address its possibilities and current limitations and the broader range of Parkinson disease features that dopamine cell replacement based on generating neurons from human pluripotent stem cells could effectively treat in the future. [Nat Rev Neurosci] Abstract

Current Challenges and Emerging Opportunities of CAR-T Cell Therapies

Besides providing an overview of the emerging CAR-technologies and current clinical applications, the major hurdles of CAR-T cell therapies are discussed, namely treatment-related life-threatening toxicities and the obstacles posed by the immunosupressive tumor-microenvironment of solid tumors, as well as the next-generation strategies currently designed to simultaneously improve safety and efficacy of CAR-T cell therapies in vivo. [J Control Release] Abstract

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Sarepta Therapeutics Announces Partnership with Roche in Territories Outside the United States for Its Investigational Micro-Dystrophin Gene Therapy for Duchenne Muscular Dystrophy, SRP-9001

Sarepta Therapeutics, Inc. announced that Sarepta and Roche have entered into a licensing agreement providing Roche exclusive commercial rights to SRP-9001, Sarepta’s investigational gene therapy for Duchenne muscular dystrophy, outside the United States. [Sarepta Therapeutics, Inc.] Press Release

Diomics Corporation and University of California, Irvine Collaborate to Enable Cell Therapy Clinical Trial for Type 1 Diabetes

Diomics Corporation and the laboratory of Dr. Jonathan Lakey, Professor of Surgery and Biomedical Research and Director of the Clinical Islet Program at the University of California, Irvine announced a Sponsored Research Agreement to ultimately improve islet transplantation for patients living with type 1 diabetes. [Diomics Corporation (GlobeNewswire, Inc.)] Press Release

Gamida Cell Announces Completion of Patient Enrollment in Ongoing Phase III Clinical Study of Omidubicel

Gamida Cell Ltd. announced that in December the company completed patient enrollment in its Phase III study of the company’s lead clinical program, omidubicel, an investigational advanced cell therapy being evaluated as a potential life-saving treatment option for patients with high-risk hematologic malignancies who are in need of a bone marrow transplant. [Gamida Cell Ltd.] Press Release

Lineage Provides Update on Patient Enrollment in Phase I/Iia Clinical Study of Opregen^® for the Treatment of Dry Age-Related Macular Degeneration

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

What CRISPR-Baby Prison Sentences Mean for Research

A Chinese court has sentenced He Jiankui, the biophysicist who announced that he had created the world’s first gene-edited babies, to three years in prison for “illegal medical practice”, and handed down shorter sentences to two colleagues who assisted him. The punishments put to rest speculation over whether the Chinese government would bring criminal charges for an act that shocked the world, and are likely to deter others from similar behaviour, say Chinese scientists. [Nature News] Editorial

A Year After the Midterm Elections, Where Are They Now?

November 2018 saw a wave of candidates from all walks of science-engineering, physics, medicine, and other life sciences-win first-time positions in the House, Senate, and state legislatures across the country. Of 20 STEM candidates running for Congressional seats that The Scientist counted last year, 10 won their races, the vast majority of them Democrats as well as political newcomers. [The Scientist] Editorial

NIH

Prospective Grant of an Exclusive Patent License: Development and Commercialization of CD19/CD22 Chimeric Antigen Receptor (CAR) Therapies for the Treatment of B-Cell Malignancies (FR Doc. No:2019-28356) Notice

Prospective Grant of an Exclusive Patent License: The Development of Autologous Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1) T Cell Receptor (TCR) for the Treatment of KK-LC-1 Expressing Human Cancer (FR Doc. No:2019-28150) Notice

NEW Emerging Cellular Therapies: Cancer and Beyond and Engineering the Genome
February 8-12, 2020
Banff, Alberta, Canada

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

NEW Postdoctoral Researchers – Cell Biology (Medicinal Bioconvergence Research Center)

Postdoctoral Scientist – Functional Pharmacology (Genentech, Inc.)

Postdoctoral Researcher – Ciliopathies and Neurogenetics (University of Alberta)

Postdoctoral Researcher – Wnt Signaling (German Cancer Research Center in the Helmholtz Association)

Technical Officer – Micro-Injectionist (European Molecular Biology Laboratory)

Junior Research Fellow – Synthetic Biology (Dresden University of Technology)

Postdoctoral Fellow – Cancer Research (BC Cancer)

Research Assistant – Cancer Research (BC Cancer)

Postdoctoral Fellow – Single Cell Genomics (BC Cancer)

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