Cell Therapy News Volume 18.17 | May 15 2017

TOP STORY

High Efficacy and Safety of Low Dose CD19-Directed CAR-T Cell Therapy in 51 Refractory or Relapsed B Acute Lymphoblastic Leukemia Patients

Researchers treated 42 primary refractory/hematological relapsed and 9 refractory minimal residual disease by flow cytometry B lymphoblastic leukemia (B-ALL) patients with optimized second generation CD19-directed CAR-T cells. The CAR-T cell infusion dosages initially ranged from 0.05 to 14 × 10⁵/kg and eventually settled at 1 × 10⁵/kg for the most recent 20 cases. [Leukemia] Abstract

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MSC-Derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis

Scientists investigated the therapeutic potential of mesenchymal stem/stromal cells (MSCs)-derived extracellular vesicles (EVs) using their established mouse models for autoimmune diseases affecting the pancreas and the eye: type 1 diabetes (T1D) and uveoretinitis (EAU). The data demonstrated that MSC-derived EVs effectively prevent the onset of disease in both T1D and EAU. [Stem Cell Reports] Full Article

Enhanced Neuroprotective Efficacy of Bone Marrow Mesenchymal Stem Cells Co-Overexpressing BDNF and VEGF in a Rat Model of Cardiac Arrest-Induced Global Cerebral Ischemia

Lentiviruses that express rat brain-derived neurotrophic factor (BDNF) exon IV or vascular endothelial growth factor (VEGF)-A were created using the bicistronic shuttle vectors of pLVX-IRES-ZsGreen1 and pLVX-IRES-tdTomato, respectively. Bone marrow-derived mesenchymal stem cells that were co-transduced with the engineered lentiviruses with co-overexpression of both BDNF and VEGF along with corresponding fluorescent protein reporters were injected via jugular vein of rats that just recovered from a cardiac arrest. [Cell Death Dis] Full Article

Matrix Elasticity-Modified Scaffold Loaded with SDF-1α Improves the In Situ Regeneration of Segmental Bone Defect in Rabbit Radius

Decellularized bone scaffold was mechanically modified by coating of collagen/hydroxyapatite mixture with optimal ratio and loaded with chemokine stromal cell-derived factor-1α (SDF-1α), in which endogenous stem cell recruitment was improved by chemokine and stem cell fate was regulated by matrix elasticity of the scaffold. [Sci Rep] Full Article

Intranasal Drug Delivery of Small Interfering RNA Targeting Beclin1 Encapsulated with Polyethylenimine (PEI) in Mouse Brain to Achieve HIV Attenuation

The bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear PEI as a gene carrier was investigated in adult mouse brain. Fluorescein isothiocyanate-labeled control siRNA delivered intranasally was found in the cytoplasm of neurons and glial cells of the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse immune reaction encountered. [Sci Rep] Full Article

Bone-Forming Peptide-2 Derived from BMP-7 Enhances Osteoblast Differentiation from Multipotent Bone Marrow Stromal Cells and Bone Formation

Bone-forming peptide-2 (BFP-2) treatment of multipotent bone marrow stromal cells (BMSCs) induced expression of active alkaline phosphatase. In addition, BFP-2 enhanced CD44 and CD51 expression levels and increased Ca²⁺ content in BMSCs. Radiography at eight weeks revealed that animals that had received transplants of BFP-2-treated BMSCs showed substantially increased bone formation compared with animals that had received BMSCs treated with BMP-7. [Exp Mol Med] Full Article

Pivotal Role of Non-Cardiomyocytes in Electromechanical and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue

Transplantation of engineered cardiac tissues (ECTs) containing 50% or 70% cardiomyocytes into a rat chronic myocardial infarction model led to a more profound functional recovery as compared with controls. Notably, transplanted ECTs showed electrical synchronization with the native heart under Langendorff perfusion. [Tissue Eng Part A] Abstract | Full Article

A New Adenovector System for Implementing Thymulin Gene Therapy for Inflammatory Disorders

The control two-vector system, termed CTV, is similar to the two-vector system (ETV) but only expresses humanized Green Fluorescent Protein (hGFP). In CHO-K1, BHK, and C2C12 cells, ETV and CTV induced a dose-dependent hGFP expression. In CHO-K1 cells, transgene expression was almost completely inhibited by doxycycline. After intracerebroventricular injection of ETV in rats, thymulin levels increased significantly in the cerebrospinal fluid and there was high hGFP expression in the ependymal cell layer. [Mol Immunol] Abstract

The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and Restores a Soft Tissue Regeneration In Vivo

The authors examined the impact of a selective centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile maintenance and investigated the effect of restoring volume in reconstruction on patients affected by soft tissue damage. [Int J Mol Sci] Full Article

Phase I/II Clinical Trial to Assess Safety and Efficacy of Intratumoral and Subcutaneous Injection of HVJ-E in Castration-Resistant Prostate Cancer Patients

Researchers conducted an open-label, single-arm, Phase I/II clinical trial in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of hemagglutinating virus of Japan envelope (HVJ-E). Patients with CRPC who were docetaxel-resistant or could not receive docetaxel treatment were eligible. [Cancer Gene Ther] Full Article

Engineering Liposomal Nanoparticles for Targeted Gene Therapy

The authors discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances. [Gene Ther] Abstract

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Homology Medicines Presents Data Demonstrating Highly Efficient, On-Target In Vivo Gene Editing Capabilities of Its Novel Human-Derived Adeno-Associated Virus Vectors

Homology Medicines, Inc. announced the presentation of preclinical data demonstrating that its nuclease-free gene editing platform can induce highly efficient and on-target gene insertion in vivo through homologous recombination. Homology’s scientists presented preclinical biodistribution data showing that the company’s novel adeno-associated virus (AAV) vectors can cross the blood brain barrier as well as data showing that the incidence of pre-existing neutralizing antibodies in humans is low compared to most other AAVs. [Press release from Homology Medicines, Inc. discussing research presented at the 2017 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, Washington, DC] Press Release

Tactiva Therapeutics Presents Positive Data on Novel Dual CD4/CD8 T Cell Receptor in Preclinical Models of Cancer

Tactiva Therapeutics announced positive data on the effects of their novel autologous cellular immunotherapy. Built on a dual enhanced adoptive cell therapy platform, the company’s engineered CD4/CD8 cells generate a durable supply of CD4 cells with direct anti-tumor activity as well as sustained helper function to CD8 T cell derived TCR-transduced effector T cells. [Press release from Tactiva Therapeutics (PR Newswire Association LLC.) discussing research presented at the 2017 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, Washington, DC] Press Release

Agilis Biotherapeutics Announces Presentation of Data from Phase I/II Trial for Treatment of AADC Deficiency

Agilis Biotherapeutics, Inc. announced that data from the company’s gene therapy, AGIL-AADC, for the treatment of Aromatic L-amino acid decarboxylase (AADC) deficiency. One-year findings in the Phase I/II study revealed that treated patients exhibited gains in motor function and showed de novo dopamine production as visualized by F-DOPA PET imaging and the emergence of dopamine metabolites. [Press release from Agilis Biotherapeutics, Inc. discussing research presented at the 2017 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, Washington, DC] Press Release

Editas Medicine Demonstrates First Achievement of In Vivo Editing in Non-Human Primate Retinas

Editas Medicine, Inc. announced results from a pre-clinical study demonstrating the first achievement of efficient editing of the CEP290 gene in the retina of non-human primates. The results of this study further reinforce Editas Medicine’s belief in the transformative potential of its candidate medicine for Leber Congenital Amaurosis type 10, an inherited retinal degenerative disease that appears in childhood and leads to blindness. [Press release from Editas Medicine, Inc. discussing research presented at the 2017 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, Washington, DC] Press Release

Sangamo Therapeutics and Pfizer Announce Collaboration for Hemophilia A Gene Therapy

Sangamo Therapeutics, Inc. and Pfizer Inc. announced an exclusive, global collaboration and license agreement for the development and commercialization of gene therapy programs for Hemophilia A, including SB-525, one of Sangamo’s four lead product candidates, which Sangamo expects will enter the clinic this quarter. [Sangamo Therapeutics, Inc.] Press Release

Capricor Therapeutics Provides Update on ALLSTAR Trial

Capricor Therapeutics, Inc. announced that a pre-specified administrative interim analysis performed on six-month follow-up data from the ALLSTAR Trial, an ongoing randomized, double-blind, placebo-controlled, 142-patient Phase II clinical trial of CAP-1002 in adults who have experienced a large heart attack with residual cardiac dysfunction, has demonstrated a low probability of achieving a statistically-significant difference in the 12-month primary efficacy endpoint of percent change from baseline infarct size as a percent of left ventricular mass, measured by cardiac magnetic resonance imaging. [Capricor Therapeutics, Inc.] Press Release

Immunomic Therapeutics Announces Exclusive License of Phase II Cancer Immunotherapy Technology Targeting Cytomegalovirus (CMV)

Immunomic Therapeutics, Inc. announced an exclusive license with Annias Immunotherapeutics, a privately held Immuno-oncology company, for rights to intellectual property related to targeting antigens of CMV in cancer as well as methods of improving cancer vaccination. This new license allows Immunomic to combine its investigational nucleic acid based immunotherapy platform, LAMP-Vax, with a patented and proprietary CMV immunotherapy platform. [Immunomic Therapeutics, Inc. (Business Wire, Inc.)] Press Release

Fibrocell Announces Data Safety Monitoring Board Recommends Continuation of Phase I/II Clinical Trial of FCX-007 for Treatment of Recessive Dystrophic Epidermolysis Bullosa

Fibrocell Science, Inc. announced that the Data Safety Monitoring Board has recommended continuation of the Phase I/II clinical trial of FCX-007 for the treatment of Recessive Dystrophic Epidermolysis Bullosa, following a review of safety data from the first patient treated. FCX-007 is a genetically-modified autologous fibroblast that encodes the gene for COL7 and is being developed in collaboration with Intrexon Corporation. [Fibrocell Science, Inc.] Press Release

New MRI Data from Asterias’ Ongoing SCiStar Clinical Study Indicates AST-OPC1 Cells Prevent Formation of Damaging Lesion Cavities in Patients Suffering Severe Spinal Cord Injury

Asterias Biotherapeutics, Inc. announced new positive serial magnetic resonance imaging (MRI) data from its ongoing AST-OPC1 SCiStar Phase I/IIa clinical trial in patients with severe spinal cord injury, including: for the five AIS-A patients in the SCiStar study treated with 10 million AST-OPC1 cells who also received a serial MRI scan at six months of follow-up, the serial MRI scans at six months indicated no sign of lesion cavities in any patient. [Asterias Biotherapeutics, Inc.] Press Release

Eyevensys Announces the First-in-Human Treatment with Its GroundBreaking EyeCET ElectroTransfection Technology for Eye Diseases

Eyevensys announced that it has successfully treated the first patient in a first-in-human Phase I/II trial of its lead candidate EYS606 for Non-Infectious Uveitis. The patient was treated in Paris, France at the Cochin Institute by Professor Antoine Brézin, the principal investigator of the trial, using the company’s novel EyeCET technology. [Eyevensys] Press Release

Longeveron Begins Enrollment of Second Cohort of Phase I Trial of Allogeneic Mesenchymal Stem Cells to Treat Alzheimer’s Disease Patients

Longeveron announced that their Phase I Alzheimer’s disease trial will proceed with enrollment at the recommendation of an independent Data Monitoring Committee which reviewed data from the trial’s safety run-in Phase. The clinical trial is designed to assess the safety, tolerability and efficacy of intravenous infusion of two different doses of Longeveron mesenchymal stem cells compared to placebo. [Longeveron (PR Newswire Association LLC.)] Press Release

Adaptimmune Announces Initiation of Study to Evaluate SPEAR T-Cell Therapy Targeting AFP in Liver Cancer

Adaptimmune Therapeutics plc announced that it has initiated the first site for its AFP SPEAR T-cell study in patients with locally advanced or metastatic hepatocellular carcinoma, the sixth most common cancer worldwide. [Adaptimmune Therapeutics plc] Press Release

FDA Grants Fast Track Designation for Celyad’s Ischemic Heart Failure Therapy, C-Cure^®

FDA granted Fast Track designation for reduction in mortality, hospitalization and improvement of quality of life in patients with chronic heart failure secondary to ischemic cardiomyopathy with baseline Left Ventricular End-Diastolic Volumes between 200 and 370ml as Fast Track Development Program. Celyad’s C-Cure^® therapy is one of the most advanced cell therapies in the heart failure segment. [Celyad] Press Release

Dr. Stephan Grupp to Lead Cellular Therapy & Transplant Section in CHOP Cancer Program

A leading pediatric oncologist at Children’s Hospital of Philadelphia (CHOP), Stephan Grupp, MD, PhD, will become Chief of the Section of Cellular Therapy and Transplant in the Hospital’s Division of Oncology. [Children’s Hospital of Philadelphia (PR Newswire Association LLC.)] Press Release

Revamped ‘Anti-Science’ Education Bills in United States Find Success

State and local legislatures in the United States are experimenting with new ways to target the topics taught in science classes, and it seems to be paying dividends. Florida’s legislature approved a bill that would enable residents to challenge what educators teach students. [Nature News] Editorial

China Cracks Down on Fake Data in Drug Trials

Those who submit faked clinical trial data might now go to jail — and in extreme circumstances, be executed — under a new interpretation of China’s criminal code. The policy shift is one of a handful of measures that China is implementing both to speed up its notoriously slow drug-approval process and to keep dangerous and ineffective drugs off the market. [Nature News] Editorial

The Secret War against Counterfeit Science

China is famous for knock-off DVDs, Louis Vuitton bags and Rolex watches. But counterfeit reagents aren’t on sale in busy public markets. They are sold through sophisticated websites, mixed in with legitimate supplies, and sourced and sold using a network of unwitting partners. [Nature News] Editorial

FDA

Pharmaceutical Distribution Supply Chain Pilot Projects; Reopening of Comment Period; Request for Information (FR Doc. No:2017-08583) Notice

Government-Owned Inventions; Availability for Licensing (FR Doc. No:2017-08596) Notice

NEW The TGF-β Superfamily: Signaling in Development and Disease
July 9-14, 2017
Lisbon, Portugal

NEW Drug Discovery & Therapy World Congress 2017
July 10-13, 2017
Boston, United States

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NEW Specialist – Cell Procurement (Celgene Corporation)

NEW Head – CAR-T Operations and Technology (Celgene Corporation)

Director – Quality Control (KBI Biopharma)

Scientist – Analytical Development (KBI Biopharma)

Lecturer – Biomedical Sciences (University of Essex)

PhD Fellow – Experimental Genetic Cardiology (Oslo University Hospital)

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

Program Director – CAR-T Cell (Servier)

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

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

Postdoctoral Fellow – Various Projects (University of Oklahoma)

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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