Cell Therapy News Volume 18.04 | Feb 6 2017

TOP STORY

A Synthetic AAV Vector Enables Safe and Efficient Gene Transfer to the Mammalian Inner Ear

Researchers demonstrated the safety and efficiency of Anc80L65, a rationally designed synthetic vector, for transgene delivery to the mouse cochlea. Ex vivo transduction of mouse organotypic explants identified Anc80L65 from a set of other adeno-associated virus (AAV) vectors as a potent vector for the cochlear cell targets. [Nat Biotechnol] Abstract | Press Release

(Ranked by impact factor of the journal)

Class I-Restricted T-Cell Responses to a Polymorphic Peptide in a Gene Therapy Clinical Trial for α-1-Antitrypsin Deficiency

Researchers described the appearance of transgene-specific T-cell responses in two subjects that were part of a Phase II trial. The patient with the more robust T-cell response, which was associated with a reduction in transgene expression, was characterized more thoroughly in this study. [Proc Natl Acad Sci USA] Abstract

Chondrogenically Primed Tonsil-Derived Mesenchymal Stem Cells Encapsulated in Riboflavin-Induced Photocrosslinking Collagen-Hyaluronic Acid Hydrogel for Meniscus Tissue Repairs

Histological assessment of in vitro and subcutaneously implanted in vivo constructs demonstrated that conditioned medium (CM)-expanded cells followed by TGF-β3 exposure resulted in highest cell proliferation, GAG accumulation, and collagen deposition. Furthermore, when implanted into meniscus defect model, CM treatment amplified the potential of TGF-β3 and induced complete regeneration. [Acta Biomater] Abstract

Intravenously Transplanted Human Bone Marrow Endothelial Progenitor Cells Engraft within Brain Capillaries, Preserve Mitochondrial Morphology, and Display Pinocytotic Activity towards BBB Repair in Ischemic Stroke Rats

Investigators evaluated via electron microscopy the ability of transplanted human bone marrow endothelial progenitor cells (hBMEPCs) to repair the blood-brain barrier (BBB) in adult Sprague-Dawley rats subjected to transient middle cerebral artery occlusion (tMCAO). ß-galactosidase pre-labeled hBMEPCs were intravenously transplanted 48 hours post-tMCAO. [Stem Cells] Abstract

Notch Activation Enhances Mesenchymal Stem Cell Sheet Osteogenic Potential by Inhibition of Cellular Senescence

Knockdown of Notch target gene Hes1 totally blocked the inhibition effect of Jagged1 on cellular senescence. The in vivo allograft transplantation data showed a significant enhanced callus formation and biomechanical properties in Notch activation cultured long-term sheet groups when compared with long-term cultured sheet without Notch activation. [Cell Death Dis] Full Article

iPS-Derived MSCs from an Expandable Bank to Deliver a Prodrug-Converting Enzyme that Limits Growth and Metastases of Human Breast Cancers

Researchers prepared a feeder stock of mesenchymal stromal cells (MSCs) from induced pluripotent stem cells (iPSs) that provided an extensively expandable source of standardized cells. They then transduced the iPS-derived MSCs to express cytosine deaminase and injected them locally into a mouse xenogeneic model of human breast cancer. [Cell Death Dis] Full Article

Intranasal Delivery of a Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function in a Mouse Multiple Sclerosis Model

ST266, the biological secretome of amnion-derived multipotent progenitor cells, contains multiple anti-inflammatory cytokines and growth factors. Intranasally administered ST266 accumulated in rodent eyes and optic nerves, attenuated visual dysfunction, and prevented retinal ganglion cell loss in experimental optic neuritis, with reduced inflammation and demyelination. [Sci Rep] Full Article

Repair of Bone Defects with Prefabricated Vascularized Bone Grafts and Double-Labeled Bone Marrow-Derived Mesenchymal Stem Cells in a Rat Model

Scientists investigated the repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model. BMSCs were separated from rat bone marrow. [Sci Rep] Full Article

Bone Marrow-Derived Mesenchymal Stem Cell-Loaded Fibrin Patches Act as a Reservoir of Paracrine Factors in Chronic Myocardial Infarction

In vivo cardiac magnetic resonance and ex vivo high-spatial resolution CMR were used to track the fate of human bone marrow-derived mesenchymal stem cell (BMSC) delivered on an epicardial scaffold and more specifically assess their potential intramyocardial migration. Fifty-seven nude rats underwent permanent coronary artery ligation. [J Tissue Eng Regen Med] Abstract

Extraneuronal Pathology in a Canine Model of CLN2 Neuronal Ceroid Lipofuscinosis after Intracerebroventricular Gene Therapy that Delays Neurological Disease Progression

Studies using a canine model demonstrated that delivery of tripeptidyl peptidase-1 (TPP1) enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. The authors hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. [Gene Ther] Full Article

An AAVrh10-CAG-CYP21-HA Vector Allows Persistent Correction of 21-Hydroxylase Deficiency in a Cyp21^−/− Mouse Model

As a monogenic disease caused by loss-of-function mutations, 21-hydroxylase deficiency (21OHD) is a potential candidate for a gene therapy (GT) approach. The first step of GT is to demonstrate positive effects of the therapeutic vector in the Cyp21^−/− mouse model. Thus researchers tested the adrenal tropism of an AAVrh10-CAG-GFP vector then attempted to correct the phenotypic and biochemical alterations in Cyp21^−/− mice using an AAVrh10-CAG-humanCYP21A2-HA vector. [Gene Ther] Abstract

Nanotechnologies in Delivery of mRNA Therapeutics Using Nonviral Vector-Based Delivery Systems

The authors summarize recent advances of existing and emerging nonviral vector-based nanotechnologies for in vitro transcribed messenger RNA (IVT-mRNA) delivery and briefly summarize the interesting but rarely discussed applications on simultaneous delivery of IVT-mRNA with DNA. [Gene Ther] Abstract

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Berkeley Lights, Inc. and Mount Sinai Expand Relationship

Berkeley Lights, Inc. (BLI) and the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai announced the continuation and expansion of their strategic relationship. The relationship focuses on the innovation and automation of cell annotation and genomics research using BLI’s platforms. [Berkeley Lights, Inc.] Press Release

Renova Therapeutics Enters into Agreement to Receive Stresscopin Investigational New Drug File from Janssen

Renova^™ Therapeutics, Inc. announced that it has entered into an agreement with Janssen Pharmaceuticals, Inc., whereby the investigational new drug file for stresscopin – a hormone involved in responses to physiological stress – will be transferred from Janssen, where it was previously under development. Renova Therapeutics plans to advance development of the stresscopin program as RT-400, a peptide infusion treatment for episodes of Acute Decompensated Heart Failure. [Renova^™ Therapeutics, Inc.] Press Release

Isogenica Announces New License Agreement with Maverick Therapeutics

Isogenica Ltd. announced a new licensing deal with Maverick Therapeutics, a private start-up biotechnology company utilizing a proprietary T-cell engagement format for the development of novel T-cell redirection therapies. Under the terms of the agreement, Isogenica has granted licenses to its family of llamdA^™ VHH single-domain antibody libraries for the discovery, development and commercialization of therapeutic products derived from these libraries. [Isogenica Ltd.] Press Release

Benitec Biopharma Makes Significant Progress in Ocular Program

Benitec Biopharma Limited announced that it has made significant progress with the company’s ddRNAi technology for the development of therapeutics for the treatment of ocular diseases. Of particular importance is the output from Benitec’s collaboration with 4D Molecular Therapeutics to identify novel viral vectors for delivery to the back of the eye using direct intravitreal injection, a commercially attractive route of administration. [Benitec Biopharma Limited (PR Newswire Association LLC.)] Press Release

MeiraGTx Awarded Target ALS Grant for Its NMD-Based Therapy for ALS

MeiraGTx announced that it has been awarded a grant from Target ALS. The grant will fund testing of a novel gene therapy approach to treat ALS that targets TDP-43, a protein that is misregulated in over 95% of all ALS patients. [MeiraGTx] Press Release

Spyryx Biosciences Announces Successful Completion of Phase I Clinical Trial for SPX-101 and Planned Phase II Initiation in Cystic Fibrosis during 2017

Spyryx Biosciences, Inc. announced the successful completion of a Phase I study for its lead compound, SPX-101, in healthy volunteers. SPX-101 is an inhaled SPLUNC1-derived peptide with a novel biological mechanism for regulating epithelial ion channels in the airway. The drug is designed to restore a natural pathway in the lung that regulates airway hydration and promotes mucociliary clearance, which is dysfunctional in cystic fibrosis. [Spyryx Biosciences (PR Newswire Association LLC.)] Press Release

Bluebird Bio Announces First Patient Treated with LentiGlobin^™ Drug Product under Amended Study Protocol in HGB-206 Phase I Study of Patients with Severe Sickle Cell Disease

bluebird bio, Inc. announced treatment of the first patient under the amended study protocol in HGB-206, the company’s Phase I study of its LentiGlobin Drug Product in patients with severe sickle cell disease. The study incorporates several changes to the study protocol with the goal of increasing production of therapeutic anti-sickling hemoglobin. [bluebird bio, Inc.] Press Release

BioMarin Receives Access to Priority Medicines (PRIME) Regulatory Support from EMA for BMN 270 Gene Therapy in Hemophilia A

BioMarin Pharmaceutical Inc. announced that the European Medicines Agency (EMA) has granted access to its Priority Medicines (PRIME) regulatory initiative for the company’s investigational gene therapy treatment for severe hemophilia A, BMN 270. To be accepted for PRIME, an investigational therapy has to show its potential to benefit patients with unmet medical needs based on early clinical data. [BioMarin Pharmaceutical Inc.] Press Release

The BBVA Foundation Distinguishes Emmanuelle Charpentier, Jennifer Doudna and Francisco Mojica, Instigators of the CRISPR “Revolution” in Genome Editing

The BBVA Foundation Frontiers of Knowledge Award in the Biomedicine category is shared, in this ninth edition, by Emmanuelle Charpentier, Jennifer Doudna and Francisco Martínez Mojica, whose pioneering work has ignited “the revolution in biology permitted by CRISPR/Cas 9 techniques.” These tools facilitate genome modification with an unprecedented degree of precision and far more cheaply and straightforwardly than any previous method. [BBVA Foundation Frontiers of Knowledge Award in Biomedicine (PR Newswire Association LLC.)] Press Release

US Government Takes Animal-Welfare Data Offline

The US Department of Agriculture agency charged with ensuring the humane treatment of large research animals, such as primates and goats, has quietly scrubbed all inspection reports and enforcement records from its website. The move has drawn criticism from animal-welfare and transparency activists who say the public has the right to know how their tax dollars are being used. [Nature News] Editorial

Venezuela Is Running Short on HIV Meds—and Places to Turn for Help

On top of its currency being in free fall for three years running, empty shelves at supermarkets, and electricity rationing, Venezuela has a serious shortage of medicines, including life-saving anti-HIV drugs. This led a network of Venezuelans living with HIV to seek “urgent humanitarian aid” in June 2016 from the Geneva, Switzerland–based Global Fund to Fight AIDS, Tuberculosis and Malaria. [ScienceInsider] Editorial

FDA

Advisory Committee Nominations; Modification To Process for Collecting and Posting Curricula Vitae (FR Doc. No:2017-02411) Notice

NEW Innovations in Cancer Research and Regenerative Medicine
September 10-17, 2017
Ho Chi Minh City, Viet Nam

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

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

Postdoctoral Researchers – Regenerative, Modular & Developmental Engineering Laboratory (NUI Galway)

Medical Director – Clinical Research Physician (Celgene Corporation)

Postdoctoral Fellow – Various Projects (University of Oklahoma)

Scientist – Regulatory Support (Cook MyoSite, Inc.)

Senior Scientist – Cell Isolation, Culture, and Genetic Engineering of Human B Cells for Expression of Therapeutic Gene Products (Immusoft Corporation)

Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame)

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

Senior Research Scientist – Otolaryngology (Vanderbilt University Medical Center)

Laboratory Technician – Cellular Production Associate II-III (Fred Hutchinson Cancer Research Center)

Staff Research Associate III – Clinical Gene, Cellular, and Other Pharmaceutical Product Manufacturing (University of California Davis Health System)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

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