Cell Therapy News Volume 18.15 | May 1 2017

TOP STORY

Targeting Genomic Rearrangements in Tumor Cells through Cas9-Mediated Insertion of a Suicide Gene

Researchers targeted the breakpoints of TMEM135–CCDC67 and MAN2A1–FER fusions in human prostate cancer or hepatocellular carcinoma cells in vitro and in mouse xenografts. They designed one adenovirus to deliver the nickase Cas9D10A and guide RNAs targeting the breakpoint sequences, and another to deliver an EGFP-HSV1-tk construct flanked by sequences homologous to those surrounding the breakpoint. [Nat Genet] Abstract | Press Release

(Ranked by impact factor of the journal)

Smartphone-Controlled Optogenetically Engineered Cells Enable Semiautomatic Glucose Homeostasis in Diabetic Mice

Using a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology, scientists engineered a technological infrastructure enabling the smartphone-assisted semiautomatic treatment of diabetes in mice. A custom-designed home server SmartController was programmed to process wireless signals, enabling a smartphone to regulate hormone production by optically engineered cells implanted in diabetic mice via a far-red light–responsive optogenetic interface. [Sci Transl Med] Abstract | Press Release

Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase II Randomized Placebo-Controlled Study (MIAS)

Investigators evaluated the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence in a controlled study. They conducted a Phase II randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM or placebo injection using Cleveland Clinic Incontinence, score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year. [Ann Surg] Abstract

Antitumoral Cascade-Targeting Ligand for IL-6 Receptor-Mediated Gene Delivery to Glioma

Transport of I₆P₇-modified but not the control nanoparticles across blood-brain barrier was demonstrated in vitro in a transwell bEnd.3 cell model resulting in transfection of underlying U87 cells, and also in vivo in glioma-bearing mice. Intravenous administration of I₆P₇-Stp-His/ pDNA encoding inhibitor of growth 4 significantly prolonged the survival time of orthotopic U87 glioma-bearing mice. [Mol Ther] Abstract

CXCR5-Overexpressing Mesenchymal Stromal Cells Exhibit Enhanced Homing and Can Decrease Contact Hypersensitivity

Scientists investigated whether genetically engineered mesenchymal stromal cells could exhibit increased migratory properties and improved therapeutic efficacy. Using a mouse model of contact hypersensitivity, chemokine gene expression screening revealed that CXCL13 changed most significantly in injured tissue. [Mol Ther] Abstract

Quantitative Assessment of Timing, Efficiency, Specificity, and Genetic Mosaicism of CRISPR/Cas9 Mediated Gene Editing of Hemoglobin Beta Gene in Rhesus Monkey Embryos

As a model gene for measuring parameters of CRISPR/Cas9 application in a primate species, investigators selected the β-hemoglobin gene, which also has high relevance to potential application of gene editing and stem-cell technologies for treating human disease. Their data demonstrated an ability to achieve a high efficiency of gene editing in rhesus monkey zygotes, with no detected off-target effects at selected off-target loci. [Hum Mol Genet] Abstract | Press Release

Functional Neuronal Differentiation of Injury-Induced Muscle-Derived Stem Cell-Like Cells with Therapeutic Implications

Scientists report that injury-induced muscle-derived stem cell-like cells (iMuSCs) have the capability to form neurospheres that represent multiple neural phenotypes. The induced neuronal cells expressed various neuron-specific proteins, their mRNA expression during neuronal differentiation recapitulated embryonic neurogenesis, they generated action potentials, and they formed functional synapses in vitro. Transplantation of iMuSCs or their cell extracts into the muscles of mdx mice could restore the morphology of their previously damaged neuromuscular junctions. [Sci Rep] Full Article

Xenotransplantation of Interferon-Gamma-Pretreated Clumps of a Human Mesenchymal Stem Cell/Extracellular Matrix Complex Induces Mouse Calvarial Bone Regeneration

Researchers investigated the effect of interferon (IFN)-γ on the immunomodulatory capacity of mesenchymal stem cell/extracellular matrix complex (C-MSC) in vitro and to test the bone regenerative activity of C-MSC or IFN-γ-pretreated C-MSC xenografts in a mice calvarial defect model. [Stem Cell Res Ther] Full Article

The Effect of Adipose Tissue-Derived Stem Cells in a Middle Cerebral Artery Occlusion Stroke Model Depends on Their Engraftment Rate

The authors investigated the effect of different doses of adipose tissue-derived stem cells on engraftment rates and stroke outcome measured in vivo using 9.4-T high-field magnetic resonance imaging. [Stem Cell Res Ther] Full Article

Improved Gene Delivery to Adult Mouse Spinal Cord through the Use of Engineered Hybrid Adeno-Associated Viral Serotypes

Scientists assessed the transduction of adult spinal cord at two different doses of adeno-associated viral vectors expressing green fluorescent protein via intraparenchymal injection at the thoracic vertebral level T9. In comparison to an equal dose of the currently preferable AAV9 serotype, Rec3 serotype transduced a broader region of spinal cord up to approximately 1.5 cm longitudinally, and displayed higher transgene expression and increased maximal transduction rates of astrocytes at either dose and neurons at the lower dose. [Gene Ther] Abstract

Spatially and Temporally Regulated NRF2 Gene Therapy Using Mcp-1 Promoter in Retinal Ganglion Cell Injury

The authors describe a temporally and spatially regulated adeno-associated virus gene therapy aiming to reduce undesired off-target effects on healthy retinal neurons. The Mcp-1 promoter previously shown to be activated in stressed retinal ganglion cells following murine optic nerve injury was combined with the neuroprotective intracellular transcription factor Nrf2. [Mol Ther Methods Clin Dev] Full Article

Cell Transplantation Therapy for Spinal Cord Injury

The transplantation of Schwann cells, neural stem cells or progenitor cells, olfactory ensheathing cells, oligodendrocyte precursor cells and mesenchymal stem cells has been investigated as potential therapies for spinal cord injury. However, little is known about the mechanisms through which these individual cell types promote repair and functional improvements. [Nat Neurosci] Abstract

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

Servier and CTI BioPharma Expand License and Collaboration Agreement to Develop and Commercialize PIXUVRI^®

Servier and CTI BioPharma Corp. jointly announced that they agreed to expand their existing license and development collaboration agreement for PIXUVRI^® (pixantrone). PIXUVRI is a cytotoxic medicine that works by interfering with the DNA within cells and preventing them from making more copies of DNA. This means that the cancer cells in B-cell NHL cannot divide and eventually die. [Servier] Press Release

Asterias Biotherapeutics Announces Data Monitoring Committee Unanimously Recommends Continuation of SCiStar Phase I/IIa Clinical Trial of AST-OPC1 for Cervical Spinal Cord Injury

Asterias Biotherapeutics, Inc. announced that following a regularly scheduled interim review of safety data from its SCiStar Phase I/IIa clinical trial of AST-OPC1 for acute spinal cord injury, the study’s Data Monitoring Committee recommended continuation of enrollment for the 10 million cell and 20 million cell dose cohorts in the study, as planned. [Asterias Biotherapeutics, Inc.] Press Release

Celyad Initiates Second Dose Escalation in THINK Trial in First US Patient

At the first solid tumor dose-level, one pancreatic and two colorectal cancer patients were successfully dosed. None of these patients experienced dose limiting adverse events. THINK is a multinational open-label Phase I study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 T-cells in seven refractory cancers including five solid tumors and two hematological tumors. [Celyad] Press Release

Cambridge Epigenetix Licenses Fundamental DNA Methylation IP from Boston Children’s Hospital

Cambridge Epigenetix announced that it has entered into an exclusive license agreement with Boston Children’s Hospital giving access to leading-edge DNA profiling technologies, which may hold the key to improved diagnoses and treatment of many diseases, including cancer. [Cambridge Epigenetix] Press Release

enGene’s Mucosal Gene Delivery Platform Is Successful in Targeting PD-L1 Expression in the Gut, Demonstrating Effective Treatment of Colitis and GvHD in Preclinical Models

enGene Inc. announced that data from preclinical studies demonstrated successful expression of programmed death-ligand 1 (PD-L1) protein in the gut showing therapeutic efficacies in mouse models of inflammatory bowel disease and graft-versus-host disease. [enGene Inc.] Press Release

CWRU’s Martin Basch Receives Prestigious Hartwell Foundation Award for Research on Congenital Deafness

Martin Basch, PhD, assistant professor of otolaryngology – head and neck surgery, has been named a recipient of a 2016 Hartwell Individual Biomedical Research Award. The award helps researchers pursue early-stage, cutting-edge biomedical pediatric research. With the award, Basch will pioneer the study of cell therapies to treat congenital strial deafness, with the goal of restoring hearing. [Case Western Reserve University] Press Release

Johns Hopkins Supporting Innovation with New Innovation Hub

The Johns Hopkins University announced the opening of its state-of-the-art innovation hub, FastForward 1812. The 23,000-square-foot space near Johns Hopkins’ flagship hospital and schools of medicine, public health and nursing provides Baltimore’s burgeoning innovation ecosystem and area startups sought-after office, co-working and wet lab space to accommodate a variety of startups. [Johns Hopkins University] Press Release

How Science Fares in the U.S. Budget Deal

Congress has finally reached a deal on spending bills for the 2017 fiscal year, which ends on 30 September. House of Representatives and Senate leaders announced last night that they expect lawmakers to vote this week on an agreement that wraps together all 12 appropriations bills that fund federal operations. For the past 7 months, the government has been operating under a continuing resolution that froze 2017 spending at most agencies at 2016 levels and generally prevented them from starting new programs. [ScienceInsider] Editorial

$10 Million Settlement over Alleged Misconduct in Boston Heart Stem Cell Lab

A research misconduct investigation of a prominent stem cell lab by the Harvard University-affiliated Brigham and Women’s Hospital in Boston has led to a massive settlement with the U.S. government over allegations of fraudulently obtained federal grants. [ScienceInsider] Editorial

Controversial UK Research Reform Crosses Finish Line

A controversial and wide-ranging shake-up of the United Kingdom’s research and higher-education landscape has been completed, amid a huge rush by the country’s parliament to push through legislation. [Nature News] Editorial

FDA

Food and Drug Administration Small Business and Industry Assistance Regulatory Education for Industry Spring Conference; Public Conference (FR Doc. No:2017-08308) Notice

Cybersecurity of Medical Devices: A Regulatory Science Gap Analysis; Public Workshop; Request for Comments (FR Doc. No:2017-08314) Notice

Issuance of Priority Review Voucher; Rare Pediatric Disease Product (FR Doc. No:2017-08309) Notice

NEW 18^th International Congress of Developmental Biology
June 18-22, 2017
Singapore, Singapore

NEW EACR-AACR-SIC Special Conference 2017: The Challenges of Optimizing Immuno- and Targeted Therapies: From Cancer Biology to the Clinic
June 24-27, 2017
Florence, Italy

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

NEW Lecturer – Biomedical Sciences (University of Essex)

NEW PhD Fellow – Experimental Genetic Cardiology (Oslo University Hospital)

GMP Manufacturing Director – Cell and Gene Therapy (Fred Hutchinson Cancer Research Center)

Program Director – CART Cell (Servier)

Research Fellow – Functional Roles of Stem Cell Derived Extracellular Vesicles (Mayo Clinic)

Executive Director – Global CAR-T Supply (Celgene Corporation)

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

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

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)

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