Cell Therapy News Volume 21.01 | Jan 13 2020

TOP STORY

GDNF Rescues the Fate of Neural Progenitor Grafts by Attenuating Notch Signals in the Injured Spinal Cord in Rodents

In a screen for potential clinically relevant factors to modulate Notch signaling, researchers identified glial cell-derived neurotrophic factor (GDNF). GDNF attenuated Notch signaling by mediating delta-like 1 homolog expression, which was independent of GDNF’s effect on cell survival. [Sci Transl Med] Abstract

(Ranked by impact factor of the journal)

Integrin-Specific Hydrogels Modulate Transplanted Human Bone Marrow-Derived Mesenchymal Stem Cell Survival, Engraftment, and Reparative Activities

Investigators showed that synthetic hydrogels presenting integrin-specific peptides enhanced the survival, persistence, and osteo-reparative functions of human bone marrow-derived mesenchymal stem cells (hMSCs) transplanted in murine bone defects. Integrin-specific hydrogels regulate hMSC adhesion, paracrine signaling, and osteoblastic differentiation in vitro. [Nat Commun] Full Article

Preclinical Development of a Humanized Chimeric Antigen Receptor Against B Cell Maturation Antigen for Multiple Myeloma

Scientists generated clinical-grade murine CART cells directed against B-cell maturation antigen, named ARI2m cells. Having demonstrated its efficacy, and in an attempt to avoid the immune rejection of CART cells by the patient, the single chain variable fragment was humanized, creating ARI2h cells. ARI2h cells demonstrated comparable in vitro and in vivo efficacy to ARI2m cells, and superiority in cases of high tumor burden disease. [Haematologica] Abstract

Single SERCA2a Therapy Ameliorated Dilated Cardiomyopathy for 18 Months in a Mouse Model of Duchenne Muscular Dystrophy

The authors injected an AAV9 human SERCA2a vector intravenously to three-month-old mdx mice, the most commonly used Duchenne muscular dystrophy model. Immunostaining and western blot showed robust human SERCA2a expression in the heart and skeletal muscle for 18-months. [Mol Ther Nucleic Acids] Abstract

Gene Therapy for Glaucoma by Ciliary Body Aquaporin 1 Disruption Using CRISPR-Cas9

Using ShH10 to deliver a single vector CRISPR-Cas9 system disrupting Aquaporin 1 resulted in reduced intraocular pressure (IOP) in treated eyes compared to control or non-injected eyes. Editing in the aquaporin 1 gene could be detected in ciliary body and no off-target increases in corneal or retinal thickness were identified. In experimental mouse models of corticosteroid and microbead-induced ocular hypertension, IOP could be reduced to prevent ganglion cell loss compared to untreated eyes. [Mol Ther Nucleic Acids] Abstract | Full Article

Pluronic-F127/Platelet Microvesicles Nanocomplex Delivers Stem Cells in High Doses to the Bone Marrow and Confers Post-Irradiation Survival

The abrogation of CXCR4/SDF-1 axis regulating the transmigration of the cells by antagonist AMD3100 revealed that the enriched CXCR4 receptors on pMVs robustize the transmigration of the infused cells. The homing of the cells led to effective engraftment and faster regeneration of the critical blood lineages, which elicited 100% survival of the mice receiving lethal doses of radiation. [Sci Rep] Full Article

Impact of ABO Incompatibility on Outcomes after Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia

A total of 199 SAA patients receiving haploidentical hematopoietic stem cell transplantation from ABO-matched, minor ABO-incompatible, or major ABO-incompatible donors were included in this study. The median time and cumulative incidences of both myeloid and platelet engraftment in the AB-compatible and ABO-incompatible groups were similar, and pure red cell aplasia was absent. [Bone Marrow Transplant] Abstract

Transposon-Mediated Generation of CAR-T Cells Shows Efficient Anti B-Cell Leukemia Response after Ex Vivo Expansion

Researchers generated 19BBz CAR-T cells in eight days using a protocol based on the non-viral transposon-based vector Sleeping Beauty. The expanded cells display mostly a central memory phenotype, expressing higher levels of inhibitory receptors when compared with mock cells. [Gene Ther] Abstract

Human Amniotic Mesenchymal Stem Cells Alleviate Paraquat-Induced Pulmonary Fibrosis in Rats by Inhibiting the Inflammatory Response

Human amniotic mesenchymal stem cells (hAMSCs) were identified by morphological, flow cytometry and immunocytochemistry. A pulmonary fibrosis model was induced by administering paraquat (PQ) to rats. The hAMSC group was treated with hAMSCs after six hours of PQ poisoning. [Life Sci] Abstract

Subscribe to one of our other 19 science newsletters such as Mesenchymal Cell News & ESC & iPSC News.

Immune Responses to Viral Gene Therapy Vectors

Investigators provide an overview of the type of immune responses that have been documented in animal models and humans that received gene transfer with one of three widely tested vector systems, namely adenoviral, lentiviral, or adeno-associated viral vectors. Particular emphasis is given to mechanisms leading to immune responses, efforts to reduce vector immunogenicity, and potential solutions to the problems. [Mol Ther] Abstract

Current Challenges and Emerging Opportunities of CAR-T Cell Therapies

The authors provide an overview of the emerging CAR-technologies and current clinical applications, and 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 | Graphical Abstract

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

BridgeBio Pharma’s Gene Therapy Subsidiaries Enter Strategic Partnership with Catalent for Dedicated Gene Therapy Development and Manufacturing Capacity

BridgeBio Pharma, Inc. announced a collaboration agreement with Catalent to establish dedicated gene therapy development and manufacturing capacity at Catalent’s Paragon Gene Therapy clinical and commercial manufacturing center in Harmans, Maryland. The agreement is intended to support the clinical and commercial manufacturing needs for BridgeBio’s gene therapy product candidates for congenital adrenal hyperplasia, BBP-631, and Canavan disease, BBP-812. [BridgeBio Pharma, Inc.] Press Release

Indapta Therapeutics and Lonza Announce Strategic Partnership to Advance a Next-Generation, Off-the-Shelf, Allogeneic Immuno-Oncology Therapy

Indapta Therapeutics, Inc. Lonza announced a strategic partnership. Indapta also announced its founding leadership team and scientific advisors. Under the terms of the agreement, Lonza will manufacture Indapta’s off-the-shelf, allogeneic G-NK cell therapy under current good manufacturing practices for use in clinical studies. [Lonza] Press Release

CYTOVIA Therapeutics and the New York Stem Cell Foundation Research Institute Enter into a Partnership to Develop iPSC Derived CAR NK Therapeutics

The New York Stem Cell (NYSCF) Foundation Research Institute announced a partnership with Cytovia Therapeutics Inc. to develop new disease treatments that leverage human stem cell research and novel gene editing techniques. NYSCF will be a key partner to Cytovia in using stem cells to advance novel therapeutic targets for cancer. [The New York Stem Cell] Press Release

Tacitus Therapeutics Launches in Collaboration with Mount Sinai to Develop Stem Cell Therapies for Life-Threatening Diseases

Tacitus Therapeutics has launched in collaboration with the Mount Sinai Health System to develop stem cell therapies initially targeting blood cancers and related clotting disorders. Their first therapy, HSC100, currently is being investigated in a Phase I clinical trial. [Tacitus Therapeutics] Press Release

Acepodia Announces FDA Clearance of IND for Its NK Cell Therapy Drug Candidate ACE1702 to Treat Patients with HER2-Expressing Solid Tumors

Acepodia announced it has received clearance of its Investigational New Drug (IND) application from the FDA to initiate a Phase I clinical study of its natural killer cell therapy and lead drug candidate ACE1702 in patients with HER2-expressing solid tumors. [Acepodia (Globe Newswire, Inc.)] Press Release

FDA and NIH Let Clinical Trial Sponsors Keep Results Secret and Break the Law

For 20 years, the US government has urged companies, universities, and other institutions that conduct clinical trials to record their results in a federal database, so doctors and patients can see whether new treatments are safe and effective. Few trial sponsors have consistently done so, even after a 2007 law made posting mandatory for many trials registered in the database. [ScienceInsider] Editorial

Predatory-Journal Papers Have Little Scientific Impact

Papers published in ‘predatory’ journals attract little attention from scientists, and get cited much less than those in reputable publications, an analysis shows. Predatory journals are those that charge authors high article-processing fees but don’t provide expected publishing services, such as peer review or other quality checks. [Nature News] Editorial

UT Austin Releases Report of 17 Employee Sexual Misconduct Cases

Officials from the University of Texas at Austin released a report Thursday, January 10 detailing 17 cases of employee sexual misconduct that took place between November 2017 and December 2019, including three faculty members and one research fellow. The allegations ranged in severity from failing to disclose a consensual relationship with a graduate student, to repeated unwelcome comments, to stalking both on- and off-campus. [The Scientist] Editorial

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

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

NEW Research Fellow – Regenerative Medicine (University of Edinburgh)

NEW Postdoctoral Researcher – Personalized Cancer Treatments (National University of Ireland Galway)

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

Postdoctoral Researchers – Cell Biology (Medicinal Bioconvergence Research Center)

Postdoctoral Scientist – Functional Pharmacology (Genentech, Inc.)

Postdoctoral Researcher – Ciliopathies and Neurogenetics (University of Alberta)

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)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Cell Therapy News? Click here to submit!

Comments or suggestions? Submit your feedback here.