Cell Therapy News Volume 19.11 | Apr 2 2018

TOP STORY

Combinatorial Effects of VEGFR Kinase Inhibitor Axitinib and Oncolytic Virotherapy in Mouse and Human Glioblastoma Stem-Like Cell Models

The authors evaluated the cytotoxic effects of VEGFR tyrosine kinase inhibitor axitinib in vitro and then tested anti-tumor efficacy of axitinib in combination with oncolytic herpes simplex virus expressing anti-angiogenic cytokine murine IL12 in two orthotopic glioblastoma (GBM) stem-like cells-derived GBM models. [Clin Cancer Res] Abstract

(Ranked by impact factor of the journal)

Improving CAR-T Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-Cell Engager

Investigators report that CAR-T cells targeting the folate receptor alpha successfully infiltrated pre-established xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. [Cancer Immunol Res] Abstract | Full Article

Development and Evaluation of an Optimal Human Single Chain Variable Fragment Derived BCMA Targeted CAR T Cell Vector

Despite a narrow range of affinity for B-cell maturation antigen (BCMA), dramatic differences in CAR T-cell expansion were observed between unique single chain variable fragments in a repeat antigen stimulation assay. These results were confirmed by screening in a multiple myeloma xenograft model, where only the top performing CARs from the repeat antigen stimulation assay eradicated disease and prolonged survival. [Mol Ther] Abstract

Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia

To confirm cell-specific gene delivery to M1 microglia, the complexes between peptide MG1 and small interfering RNA (siRNA)-interferon regulatory factor 5 were prepared and intrathecally injected into a mouse model of neuropathic pain. [Mol Ther Nucleic Acids] Full Article

Stromal Cell-Derived Factor-1α-Encapsulated Albumin/Heparin Nanoparticles for Induced Stem Cell Migration and Intervertebral Disc Regeneration In Vivo

Researchers prepared albumin/heparin nanoparticles as injectable carriers of stromal cell-derived factor-1α, a powerful chemoattractant for the homing of bone marrow resident mesenchymal stem cells, for protection of the molecule against degradation for a sustained release. [Acta Biomater] Abstract | Graphical Abstract

FSTL3 Enhances the Function of Endothelial Cells Derived from Pluripotent Stem Cells by Facilitating β-Catenin Nuclear Translocation through Inhibition of GSK3β Activity

The angiogenic potential of follistatin-like 3 (FSTL3) was confirmed both in vitro and in vivo. When induced pluripotent stem-endothelial cells overexpressing FSTL3 were subcutaneously injected in in vivo angiogenic model or intramuscularly injected in a hindlimb ischemia NOD.CB17-Prkdcscid/NcrCrl SCID mice model, FSTL3 significantly induced angiogenesis and blood flow recovery, respectively. [Stem Cells] Abstract

Biology of the Adrenal Gland Cortex Obviates Effective Use of Adeno-Associated Virus Vectors to Treat Hereditary Adrenal Disorders

Researchers administered intravenously an adeno-associated virus serotype rh.10 gene transfer vector to 21-hydroxylase deficient mice (21OH^−/−). They demonstrated that a single intravenous administration efficiently transduced adrenocortical cells leading to 21OH-HA expression and restoration of normal steroidogenesis. [Hum Gene Ther] Full Article

Targeted In Vivo Knock-In of Human Alpha-1-Antitrypsin cDNA Using Adenoviral Delivery of CRISPR/Cas9

To test if adenoviral vectors can facilitate long-term gene expression through targeted integration, scientists somatically incorporated the human alpha-1-antitrypsin gene into the ROSA26 “safe harbor” locus in murine livers, using CRISPR/Cas9. [Gene Ther] Full Article | Press Release

Mesenchymal Stem Cell Seeded, Biomimetic 3D Printed Scaffolds Induce Complete Bridging of Femoral Critical Sized Defects

3D printed biomimetic scaffolds were used to facilitate rapid bone bridging in critical sized defects in a sheep model. Mesenchymal stem cells (MSCs) were isolated from sheep inguinal and tail fat in one group of sheep, and scaffolds were infiltrated with MSCs in a bioreactor. [J Biomed Mater Res B Appl Biomater] Abstract

Subchondral Stem Cell Therapy versus Contralateral Total Knee Arthroplasty for Osteoarthritis following Secondary Osteonecrosis of the Knee

With the hypothesis that subchondral bone marrow injection might improve knees in patients, researchers evaluated 30 patients who had bilateral knee osteoarthritis with severe joint space narrowing and received total knee arthroplasty in one knee and subchondral bone marrow concentrate injection in the contralateral knee. [Int Orthop] Abstract

CRISPR-Cas9 Genome Engineering: Treating Inherited Retinal Degeneration

The authors discuss the current developments in CRISPR-Cas9 gene editing in vivo in animal models and in vitro in patient-derived cells to study and treat inherited retinal degenerative diseases. [Prog Retin Eye Res] Abstract

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

Celyad to Present Updates on CYAD-01

Celyad announced that the company will present updates on its ongoing Phase I clinical trials. [Press release from Celyad discussing research to be presented at the 2018 American Association for Cancer Research (AACR) Annual Meeting, Chicago] Press Release

bluebird bio and Celgene Corporation Enter into Agreement to Co-Develop and Co-Promote Anti-BCMA CAR T Cell Therapy bb2121 in the United States

bluebird bio, Inc. and Celgene Corporation announced that the companies have entered into an agreement to co-develop and co-promote bb2121, an investigational anti-B-cell maturation antigen (BCMA) CAR T cell therapy for the potential treatment of patients with relapsed/refractory multiple myeloma in the United States. [bluebird bio, Inc.] Press Release

Mesoblast Phase III Cell Therapy Trial for Chronic Low Back Pain Completes Enrollment

Mesoblast Limited announced that enrollment has completed in the Phase III trial evaluating a single intra-discal injection of its proprietary allogeneic mesenchymal precursor cell (MPC) product candidate MPC-06-ID in patients with chronic low back pain due to degenerative disc disease. [Mesoblast Limited] Download Press Release

BrainStorm Cell Therapeutics’ Phase III Trial of NurOwn^® in ALS Now Open to Canadian Patients

BrainStorm Cell Therapeutics Inc. announced that it has amended the protocol of its Phase III clinical trial of NurOwn^® for the treatment of amyotrophic lateral sclerosis (ALS). [BrainStorm Cell Therapeutics Inc.] Press Release

Enrollment Completed in ADRESU Clinical Trial of Cytori Cell Therapy™ for Stress Urinary Incontinence

Cytori Therapeutics, Inc. announced that full enrollment has been reached in the ADRESU investigator-initiated clinical trial of Cytori Cell Therapy™ for men with stress urinary incontinence as a complication of prostate intervention. [Cytori Therapeutics, Inc.] Press Release

TiGenix and Takeda Announce Alofisel^® (Darvadstrocel) Receives Approval to Treat Complex Perianal Fistulas in Crohn’s Disease in Europe

TiGenix NV and Takeda Pharmaceutical Company Limited announced that the European Commission has approved Alofisel, previously Cx601, for the treatment of complex perianal fistulas in adult patients with nonactive/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. [TiGenix NV] Press Release

Krystal Submits Investigational New Drug (IND) Application for KB103, Topical Gene Therapy Candidate for Dystrophic Epidermolysis Bullosa

Krystal Biotech Inc. announced the submission of an IND application with the FDA to initiate a Phase I/II, first in-human trial of KB103, an HSV-1 based gene therapy engineered to deliver a human collagen-producing gene to patients with dystrophic epidermolysis bullosa. [Krystal Biotech Inc.] Press Release

FDA Grants Orphan Drug Designation to Cynata’s Lead Cymerus™ MSC Product, CYP-001

Cynata Therapeutics Limited announced that the FDA has granted Cynata Orphan Drug Designation for CYP-001 for the treatment of acute graft versus host disease. [Cynata Therapeutics Limited (GlobeNewswire, Inc.)] Press Release

AveXis Gene Therapy Awarded SAKIGAKE Designation for Spinal Muscular Atrophy Type 1

AveXis, Inc. announced that Japan’s Ministry of Health, Labour and Welfare awarded the company’s initial product candidate, AVXS-101, SAKIGAKE Designation for the treatment of spinal muscular atrophy type 1. [AveXis, Inc.] Press Release

Multiple Myeloma Research Foundation (MMRF) Awards $7 Million to Advance Cutting-Edge Immunotherapy Initiative

The MMRF announced that, as part of its $15M Immunotherapy Initiative, it has awarded $7M in funding to three ground-breaking research programs led by renowned myeloma researchers. [Multiple Myeloma Research Foundation] Press Release

PharmaCyte Ships Clinical Trial Cells to Austrianova for Encapsulation

PharmaCyte Biotech, Inc. announced that vials of cells from PharmaCyte’s Master Cell Bank have been shipped by Eurofins Lancaster Laboratories to Austrianova’s encapsulation facility in Thailand. [PharmaCyte Biotech, Inc.] Press Release

Sumitomo Dainippon Pharma Co., Ltd. Chooses Cytonome’s Gigasort^® Cell Sorting Technology for Cell Bioprocessing

Sumitomo Dainippon Pharma Co., Ltd. has installed the GigaSort^® Platform in their newly opened Manufacturing Plant for Regenerative Medicine & Cell Therapy in Osaka, Japan. [Sumitomo Dainippon Pharma Co., Ltd.] Press Release

Texas Stem Cell Law Opens Door for Controversial Treatments

Celltex claims to use patients’ own mesenchymal stem cells (MSCs) to treat diseases as wide-ranging as amyotrophic lateral sclerosis, renal failure, and chronic obstructive pulmonary disease. But the company had to cease offering such treatments in Texas in 2013 after the FDA sent Celltex a warning letter in 2012 stating that the patient-derived cells it was harvesting and injecting were considered drugs under US federal law, thereby requiring clinical trials and regulatory approval. But with a newly passed law in Texas known as “Charlie’s Law,” Celltex might have the opportunity to resume treating patients stateside. The new law could allow Texas clinics to administer certain non-FDA-approved stem cell treatments, like those offered by Celltex, to select patients. [The Scientist] Editorial

CRISPR May Not Cause Hundreds of Rogue Mutations After All

A scientific journal has retracted a controversial paper that suggested the gene-editing tool CRISPR was a genome wrecking ball. In the retracted study, researchers sought to use CRISPR in mice to correct a mutation that causes blindness. They successfully fixed the genetic error but reported that CRISPR inadvertently made more than a thousand other changes—potentially harmful ones—in the animals’ DNA. [MIT Technology Review] Editorial

In Emotional Speech, CDC’s New Leader Vows to Uphold Science

Robert Redfield Jr., the new director of the Centers for Disease Control and Prevention (CDC), gave a deeply personal agencywide address in which he repeatedly underscored the importance of science and data and said the CDC’s most critical public health mission is to protect Americans “from that which we don’t expect.” [The Washington Post] Editorial

Cancer Researcher at the Ohio State University Resigns following Multiple Misconduct Findings

A cancer researcher has resigned from The Ohio State University in Columbus after the institution determined he had committed misconduct in eight papers. His work in designing anticancer compounds had led to millions of dollars in funding and multiple patents, as well as two compounds in clinical trials. [ScienceInsider] Editorial

NIH Moves to Punish Researchers Who Violate Confidentiality in Proposal Reviews

Late last year, National Institutes of Health (NIH) officials disclosed that they had discovered that someone involved in the proposal review process had violated confidentiality rules designed to protect its integrity. As a result, the agency announced in December 2017 that it would re-review dozens of applications that might have been compromised. Now, NIH says it has completed re-evaluating 60 applications and has also begun taking disciplinary action against researchers who broke its rules. [ScienceInsider] Editorial

India Taps Biologist as New Science Adviser

India has a new science adviser. Prime Minister Narendra Modi’s government tapped Krishnaswamy VijayRaghavan, a molecular biologist and head of India’s Department of Biotechnology, to fill the post. [ScienceInsider] Editorial

FDA

2018 Center for Biologics Evaluation and Research Science Symposium (FR Doc. No:2018-05805) Notice

NEW NSAS Course: Cell-Reprogramming Technology in Neuroscience
May 19-26, 2018
Venice, Italy

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

NEW Scientist – Discovery Biology (Prevail Therapeutics)

NEW Postdoctoral Research Fellow – Cell/Gene Therapy (Stanford University)

Postdoctoral Fellow – CAR T (City of Hope)

Postdoctoral Fellow – Precision Therapy of Aggressive Lymphoma (AstraZeneca)

Postdoctoral Fellow – Leukemia (Necker Institut Enfants Malades)

Assistant Professor – Translation of Preclinical Regenerative Medicine into Advanced Therapy Medicinal Products (Lund University)

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 Fellow – Cancer Research (Indiana University School of Medicine)

Postdoctoral Associate – Cardiovascular Science (Duke University)

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.