Cell Therapy News Volume 18.10 | Mar 27 2017

TOP STORY

Nrl Knockdown by AAV-Delivered CRISPR/Cas9 Prevents Retinal Degeneration in Mice

Researchers report a genome editing approach in which adeno-associated virus (AAV)-mediated CRISPR/Cas9 delivery to postmitotic photoreceptors is used to target the Nrl gene, encoding for Neural retina-specific leucine zipper protein, a rod fate determinant during photoreceptor development. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Rational Combination of Oncolytic Vaccinia Virus and PD-L1 Blockade Works Synergistically to Enhance Therapeutic Efficacy

Scientists hypothesized that an oncolytic poxvirus would attract T cells into the tumor, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Their results demonstrated in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumor. [Nat Commun] Full Article

Therapeutic Efficacy of Neural Stem Cells Originating from Umbilical Cord-Derived Mesenchymal Stem Cells in Diabetic Retinopathy

The authors evaluated the effects of intravitreal injection of neural stem cells (NSCs) originating from human umbilical cord-derived mesenchymal stem cells on neurodegeneration of diabetic retinopathy in rats. Treatment of diabetic rats with NSCs prevented the decrease in BDNF levels caused by diabetes. The average leakage of Evans Blue dye in the treated group was significantly less than that in the control group. [Sci Rep] Full Article

High Plasma Lipid Levels Reduce Efficacy of Adenovirus-Mediated Gene Therapy

Researchers hypothesized that high lipid levels and specific lipoproteins could significantly decrease adenoviral transduction efficiency in vivo. They demonstrated that mice on a high fat diet have lower transgene expression compared to mice on a regular chow. In addition, on a high fat diet, ApoE^−/− mice have much higher plasma transgene levels compared to LDLR-deficient mice. [Sci Rep] Full Article

Surface Micromorphology of Cross-Linked Tetrafunctional Polylactide Scaffolds Inducing Vessel Growth and Bone Formation

The authors developed a synthetic strategy allowing a gradual variation of a polylactide arms’ length, which later influences the micromorphology of the scaffold surface, formed by a two-photon polymerization technique. PLA760 scaffolds were implanted into a created cranial defect in a mouse for an in vivo assessment of the bone tissue formation. [Biofabrication] Abstract

Haplo-Cord Transplantation Compared to Haploidentical Transplantation with Post-Transplant Cyclophosphamide in Patients with AML

Researchers analyzed outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide between 2012 and 2014 in GETH centers. [Bone Marrow Transplant] Abstract

AAV9-Mediated Engineering of Autotransplanted Kidney of Non-Human Primates

Scientists generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. AAV9-LEA29Y was able to transduce the kidney of non-human primates in an auto-transplantation model. Expression of LEA29Y mRNA by renal cells translated into the production of the corresponding protein, which was confined to the graft but not detected in serum. [Gene Ther] Abstract

Optimization of Adeno-Associated Virus Vector-Mediated Gene Transfer to the Respiratory Tract

An efficient adeno-associated virus (AAV) vector was constructed for the treatment of respiratory diseases. AAV serotypes, promoters, and routes of administration potentially influencing the efficiency of gene transfer to airway cells were examined in the present study. Among the nine AAV serotypes screened in vitro and four serotypes evaluated in vivo, AAV6 showed the strongest transgene expression. [Gene Ther] Abstract

Middle Ear Mucosal Regeneration by Tissue-Engineered Cell Sheet Transplantation

Investigators developed a novel treatment method combining tympanoplasty and autologous nasal mucosal epithelial cell sheet transplantation for postoperative regeneration of the middle ear mucosa. Tissue-engineered autologous nasal mucosal epithelial cell sheets were fabricated by culturing the harvested cells in an aseptic environment in a good manufacturing practice-compliant cell processing facility. The cultivated cell sheets were transplanted, during tympanoplasty, onto the exposed bony surface of the attic of the tympanic and mastoid cavities where the mucosa had been lost. [NPJ Regen Med] Full Article

Delivery Technologies for Genome Editing

Researchers discuss the principles of biomacromolecule delivery and gene editing, examine recent advances and challenges in non-viral and viral delivery methods, and highlight the status of related clinical trials. [Nat Rev Drug Discov] Abstract

Pluripotent Stem Cells in Neuropsychiatric Disorders

The authors review recent progress in using induced pluripotent stem cell technology to model and potentially treat neuropsychiatric disorders by focusing on the most prevalent conditions in psychiatry, including depression, anxiety disorders, bipolar disorder and schizophrenia. [Mol Psychiatry] Full Article

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

OncoSec Medical’s Intratumoral Plasmid IL-12 Demonstrates Effectiveness at Enhancing Tumor Immunogenicity in Preclinical Tumor Models

OncoSec Medical Incorporated presented a poster titled “Intratumoral Electroporation-mediated IL-12 Gene Therapy Can Enhance Tumor Immunogenicity” (Poster #2074). The poster included preclinical data demonstrating that in vivo electroporation of intratumoral plasmid IL-12 enhances immunogenicity in poorly immunogenic mouse cancer models. [Press release from OncoSec Medical Incorporated discussing research presented at Keystone Symposia Conference: Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology, Whistler] Press Release

Research Outlining Medically Actionable Approach, Patient Experiences in Pilot Program Presented

Invitae Corporation announced it has expanded the menu of tests offered as part of its ongoing proactive genetic testing pilot program. The announcement was made and researchers presented findings from the company’s growing body of experience on the use of proactive testing. [Press release from Invitae Corporation discussing research presented at the 2017 American College of Medical Genetics (ACMG) Annual Clinical Genetics Meeting, Phoenix] Press Release

Aprea Therapeutics Announces Research Collaboration with Memorial Sloan Kettering Cancer Center

Aprea Therapeutics announced a collaboration with Memorial Sloan Kettering Cancer Center to study the effects of reactivation of tumor suppressor protein p53 by APR-246. The goal of the collaboration is to evaluate and characterize preclinical efficacy of APR-246 in combination with multiple other anti-cancer agents and across multiple tumor types. [Aprea Therapeutics] Press Release

Vium Announces Co-Development Partnership with Japan’s CIEA for Humanized Disease Models

Vium announced a partnership with Japan’s Central Institute for Experimental Animals (CIEA) to co-develop humanized mouse models of disease which Vium will offer as a fee-for-service to clients around the world. The partnership, which will initially focus on developing a humanized mouse model for graft-versus-host disease using the Institute’s patented NOG^® mice [Vium] Press Release

Update on Full Six-Patient Cohort Confirms Patients with Complete Paralysis Can Experience Meaningful Recovery of Function by Six Months Following AST-OPC1 Treatment

Asterias Biotherapeutics, Inc. reported that including the sixth and final patient in the AIS-A 10 million cell cohort in the company’s ongoing SCiStar Phase I/IIa clinical trial has further confirmed previously-announced motor function improvements at six-months following administration of AST-OPC1. [Asterias Biotherapeutics, Inc.] Press Release

OPKO Receives FDA Orphan Drug Status for Its New Oligonucleotide to Treat Genetic Neurological Disorder

OPKO Pharmaceuticals LLC announced that the company has received orphan drug designation from the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development for OPKO’s oligonucleotide-based AntagoNAT (CUR-1916) for the treatment of Dravet Syndrome. OPKO Health received orphan drug designation for CUR-1916 for the treatment of Dravet Syndrome from the European Commission. [OPKO Pharmaceuticals LLC] Press Release

Gamida Cell Receives Additional EMA Orphan Drug Designation for NiCord^® in Hematopoietic Stem Cell Transplantation (HSCT)

Gamida Cell announced that orphan drug designation has been granted by the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord^® as a treatment for hematopoietic stem cell transplantation, also commonly known as bone marrow transplantation. [Gamida Cell] Press Release

Genedrive^® HCV Assay Submitted for CE IVD Certification

Genedrive plc announced submission of its Genedrive^® Hepatitis C (HCV) ID Kit for CE IVD certification under the EU Medical Devices Directive. Receipt of CE IVD certification will allow commercialization of the product within the EU and in resource limited countries in the rest of the world that accept CE certification under their national regulations. [Genedrive plc] Press Release

City of Hope’s Dr. Linda Malkas Appointed to Stem Cell Agency Board

Linda Malkas, Ph.D., Deputy Director of the City of Hope’s Comprehensive Cancer Center, has been appointed to the governing Board of the California Institute for Regenerative Medicine, the state’s Stem Cell Agency. [California Institute for Regenerative Medicine] Press Release

Election Chaos at Russian Academy of Sciences

Academics at Russia’s premier science body have been left shocked and confused after an election that was supposed to determine the new president of the Russian Academy of Sciences was cancelled at the last minute. [Nature News] Editorial

NIH Enables Investigators to Include Draft Preprints in Grant Proposals

Researchers should feel free to include preprints, or draft manuscripts that haven’t yet been gone through peer review, as part of their applications when they seek funding from the National Institutes of Health (NIH), the agency announced. [ScienceInsider] Editorial

Data Check: NSF Sends Congress a Garbled Message on Misconduct Numbers

When a senior National Science Foundation (NSF) official told the House of Representatives science committee this month about a “significant rise in the number of substantive allegations” of research misconduct, her testimony set off alarm bells. Legislators from both parties were clearly disturbed by this trend, which had led to three dozen findings of misconduct a year, and asked what the NSF was doing about it. [ScienceInsider] Editorial

FDA

Delayed Graft Function in Kidney Transplantation: Developing Drugs for Prevention; Draft Guidance for Industry; Availability (FR Doc. No:2017-05818) Notice

NEW 6^th China-Europe Symposium on Biomaterials in Regenerative Medicine
May 21-24, 2017
Porto, Portugal

NEW Advances in Stem Cells and Regenerative Medicine
May 23-26, 2017
Heidelberg, Germany

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

NEW Postdoctoral Associate – Gene Therapy (University of Massachusetts Medical School)

Research Associate – Stem Cell Depletion for the Preservation of Regenerative Fitness (University of Bristol)

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

Postdoctoral Fellow – Radioprotectant to Alleviate Physiological Damage Due to Ionizing Radiation Exposure (Canadian Nuclear Laboratories)

Postdoctoral Fellow – Gene and Stem Cell Therapy Program (Centenary Institute)

Research Scientist – Immunotherapies for Cancer (GammaDelta Therapeutics Limited)

Postdoctoral Research Fellow – Preclinical Models of Cancer Immunotherapy (Providence Cancer Center)

Principle Investigator and Postdoctoral Positions – Various Projects (Guangzhou Women and Children’s Medical Center)

BIH Chair for Cell and Gene Therapy and Coordinator of the Advanced Therapies Program (Berlin Institute of Health)

Assistant Professor – Medicine by Design Junior Chair in Immunobioengineering (University of Toronto)

Associate/Full Professor – Loretta Rogers Chair in Immunobioengineering (University of Toronto)

Medical Director – Clinical Research Physician (Celgene Corporation)

Postdoctoral Fellow – Various Projects (University of Oklahoma)

Staff Research Associate III – Translational Research to Clinical Cell Therapies (University of California Davis Health System)

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.

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

Comments or suggestions? Submit your feedback here.