Cell Therapy News Volume 17.41 | Nov 14 2016

TOP STORY

Local and Transient Gene Expression Primes the Liver to Resist Cancer Metastasis

Researchers developed a lipid calcium phosphate nanoparticle optimized for delivering plasmid DNA, encoding an engineered CXCL12 protein trap, to the nucleus of liver hepatocytes. This pCXCL12-trap formulation yielded transient liver-specific expression, which greatly decreased the occurrence of liver metastasis in two aggressive liver metastasis models, including colorectal and breast cancers. [Sci Transl Med] Abstract

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Domain-Swapped T Cell Receptors Improve the Safety of TCR Gene Therapy

Investigators report a general strategy to prevent tumor-specific αβ T cell receptor (TCR) mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped TCRs assembled with CD3, expressed on the cell surface, and mediated antigen-specific T cell responses. [eLife] Full Article | Press Release

Intrapleural Adenoviral-Mediated Endothelial Cell Protein C Receptor Gene Transfer Suppresses the Progression of Malignant Pleural Mesothelioma in a Mouse Model

Researchers investigated the mechanism by which endothelial cell protein C receptor (EPCR) suppresses malignant pleural mesothelioma (MPM) tumor growth and evaluated whether EPCR gene therapy could suppress the progression of MPM in a mouse model of MPM. Measurement of cytokines from the pleural lavage showed that mice implanted with MPM cells expressing EPCR had elevated levels of IFNγ and TNFα compared to mice implanted with MPM cells lacking EPCR. [Sci Rep] Full Article

VEGF Released by Deferoxamine Preconditioned Mesenchymal Stem Cells Seeded on Collagen-GAG Substrates Enhances Neovascularization

Investigators compared the wound healing capabilities of adipose derived mesenchymal stem cells seeded on a collagen-glycosaminoglycan dermal substrate exposed to either environmental hypoxia or FDA approved deferoxamine mesylate to stabilize HIF-1α for wound healing. [Sci Rep] Full Article

Tumor Specific Delivery and Therapy Mediate by Integrin β6-Target Immunoliposomes for β6-SiRNA in Colon Carcinoma

Researchers designed Integrinβ6 target immunoliposomes for highly efficient and selective delivery of β6-siRNA in colon cancer, which consequently resulted in great growth suppression, invasion and metastasis of colon cancer cells. Moreover, it was able to greatly inhibit the tumor growth in vivo. [Oncotarget] Full Article

In Vivo Human Adipose-Derived Mesenchymal Stem Cell Tracking after Intra-Articular Delivery in a Rat Osteoarthritis Model

Scientists aimed to understand in vivo biodistribution of clinical-grade human adipose-derived mesenchymal stem cells (haMSCs) labeled with fluorescent dye and injected into an immunocompetent osteoarthritis rat model. [Stem Cell Res Ther] Full Article

Transplantation of Gingiva-Derived Mesenchymal Stem Cells Ameliorates Collagen-Induced Arthritis

Investigators aimed to test whether transplantation of mesenchymal stem cells derived from gingival tissue could ameliorate collagen-induced arthritis, and to explore the role of the FasL/Fas pathway in the underlying mechanism. [Arthritis Res Ther] Full Article

Effect of Sustained PDGF Non-Viral Gene Delivery on Repair of Tooth-Supporting Bone Defects

A novel gene activated matrix delivering polyplexes of polyethylenimine (PEI)-plasmid DNA encoding platelet-derived growth factor (PDGF) was evaluated for promotion of periodontal wound repair in vivo. PEI-pPDGF-B polyplexes were tested in human periodontal ligament fibroblasts and gingival fibroblasts for cell viability and transfection efficiency. [Gene Ther] Abstract

The Antitumor Efficacy of Anti-p21Ras ScFv Mediated by the Dual-Promoter-Regulated Recombinant Adenovirus KGHV300

To enhance the anti-tumor efficacy and safety of anti-p21Ras scFv, the authors constructed a dual-promoter-regulated recombinant adenovirus KGHV300 that carried anti-p21Ras scFv. In KGHV300, the expression levels of the essential replication genes; i.e., E1a and E1b, were controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively, and the anti-p21Ras scFv gene was controlled by the cytomegalovirus promoter. [Gene Ther] Abstract

Preclinical Development and Qualification of ZFN-Mediated CCR5 Disruption in Human Hematopoietic Stem/Progenitor Cells

A strategy to disrupt chemokine receptor 5 (CCR5) genomic sequences in hematopoietic stem/progenitor cells (HSPC) using zinc finger nucleases was developed. Following discussions with regulatory agencies, scientists conducted IND-enabling preclinical in vitro and in vivo testing to demonstrate the feasibility and safety of zinc finger nucleases-based CCR5 disruption in HSPC. [Mol Ther Methods Clin Dev] Full Article

Skin-Derived Stem Cells as a Source of Primordial Germ Cell- and Oocyte-Like Cells

The authors discuss the origin and characteristics of skin-derived stem cells (SDSCs) from which the germ cell-like cells (GCLCs) are derived, the possible mechanisms of this differentiation process, and finally the prospective biomedical applications of the SDSC-derived GCLCs. [Cell Death Dis] Full Article

Imaging Techniques: New Avenues in Cancer Gene and Cell Therapy

Molecular imaging, such as nanosystems, fluorescence, bioluminescence, positron emission tomography, single photon-emission computed tomography and magnetic resonance imaging, have been found to be powerful tools in monitoring cancer patients who have received therapeutic cell and gene therapies or drug therapies. [Cancer Gene Ther] Abstract

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Arrowhead Pharmaceuticals Presents New Data on ARC-F12 and ARC-LPA Using DPC_sq^TM Subcutaneous RNAi Delivery Vehicle

Arrowhead Pharmaceuticals, Inc. delivered oral presentations on ARC-LPA, its preclinical development program targeting lipoprotein, for the treatment of cardiovascular disease, and ARC-F12, its preclinical development program targeting factor XII (F12) for the prophylactic treatment of thromboembolism and hereditary angioedema. [Press release from Arrowhead Pharmaceuticals, Inc. discussing research presented at the American Heart Association’s Scientific Sessions 2016, New Orleans] Press Release

Arrowhead Pharmaceuticals Presents New Data on ARC-AAT

Arrowhead Pharmaceuticals, Inc. delivered a poster presentation with Phase I clinical data and an oral presentation with preclinical data on ARC-AAT, its investigational medicine for the treatment of liver disease associated with alpha-1 antitrypsin deficiency (AATD). The data indicate that in a first-in-human clinical study, ARC-AAT was well tolerated and induced deep and durable reduction of the target AAT protein. [Press release from Arrowhead Pharmaceuticals, Inc. discussing research presented at the 2016 American Association for the Study of Liver Diseases (AASLD) Liver Meeting, Boston] Press Release

Promethera Biosciences Provides Update on HepaStem NASH-Fibrosis Program with Late-Breaking Preclinical Data

Promethera Biosciences SA announced the presentation of new preclinical NASH-Fibrosis data from its proprietary HepaStem program, demonstrating a beneficial effect of HepaStem in a nonalcoholic steatohepatitis (NASH) mouse model and confirming Hepastem’s unique and multifaceted mode of action. [Press release from Promethera Biosciences SA discussing research presented at the 2016 American Association for the Study of Liver Diseases (AASLD) Liver Meeting, Boston] Press Release

bluebird bio to Present New Data from Novel Anti-BCMA CAR T Cell Therapy bb2121

bluebird bio, Inc. announced that interim data from its study of bb2121, the company’s anti-BCMA CAR T cell therapy, currently in a Phase I trial of patients with relapsed/refractory multiple myeloma will be presented. [Press release frombluebird bio, Inc. discussing research to be presented at the 28^th EORTC-NCI-AACR Molecular Targets and Cancer Therapies Symposium, Munich] Press Release

MiNA Therapeutics Presents Data Demonstrating Survival Benefit of MTL-CEBPA in Animal Model of Liver Failure

MiNA Therapeutics announced the presentation of pre-clinical data on its MTL-CEBPA program in which the compound was shown to improve survival in a rat model of liver failure. MTL-CEBPA is the first development candidate to emerge from MiNA’s RNA activation platform and is currently being evaluated in a Phase I clinical study in patients with liver cancer. [Press release from MiNA Therapeutics discussing research presented at the 2016 American Association for the Study of Liver Diseases (AASLD) Liver Meeting, Boston] Press Release

Nektar Therapeutics Presents New Clinical Data from Ongoing Phase I Dose-Escalation Study of NKTR-214

Nektar Therapeutics announced that new Phase I clinical data for Nektar’s lead immuno-oncology agent, NKTR-214, were presented. NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting T cells and Natural Killer cell abundance directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. [Press release from Nektar Therapeutics discussing research presented at the Society for Immunotherapy of Cancer (SITC) 2016 Annual Meeting, National Harbor] Press Release

Alnylam Pharmaceuticals Announces Sanofi Genzyme Opt-In Decision for Co-Development and Co-Commercialization of Fitusiran in Hemophilia and Rare Bleeding Disorders

Alnylam Pharmaceuticals, Inc. announced that Sanofi Genzyme elected to opt in to co-develop and co-commercialize fitusiran, an investigational RNAi therapeutic for the treatment of hemophilia and rare bleeding disorders, in the United States, Canada and Western Europe. [Alnylam Pharmaceuticals, Inc.] Press Release

Biogen and Ionis Pharmaceuticals Announce SPINRAZA (Nusinersen) Meets Primary Endpoint at Interim Analysis of Phase III CHERISH Study in Later-Onset Spinal Muscular Atrophy

Biogen and Ionis Pharmaceuticals announced that SPINRAZA^™, an investigational treatment for spinal muscular atrophy (SMA), met the primary endpoint at the interim analysis of CHERISH, the Phase III study evaluating SPINRAZA in later-onset SMA. The analysis found that children receiving SPINRAZA experienced a highly statistically significant improvement in motor function compared to those who did not receive treatment. [Biogen] Press Release

RegeneRx Announces First Patients Enrolled in Phase III U.S. Dry Eye Clinical Trial (ARISE-2 Trial) with RGN-259

RegeneRx Biopharmaceuticals, Inc. announced that the first patients have been enrolled in a Phase III clinical trial with RGN-259 (Thymosin beta 4), its sterile, preservative-free eye drop formulation developed for patients with dry eye syndrome, neurotrophic keratopathy, and other corneal disorders. [RegeneRx Biopharmaceuticals, Inc.] Press Release

Arrowhead Pharmaceuticals Provides Update on Heparc-2004 Study

Arrowhead Pharmaceuticals, Inc. provided an update on its Heparc-2004 clinical study of ARC-520, its therapeutic candidate under clinical investigation for the treatment of chronic hepatitis B virus infection. Heparc-2004 is a multicenter, randomized, double-blind, placebo-controlled, multi-dose study of ARC-520, which is currently being performed in up to 12 patients in the United States under an Investigational New Drug. [Arrowhead Pharmaceuticals, Inc.] Press Release

Avellino Labs to Introduce Keratoconus Screening Test in Early 2017

Avellino Labs announced that it will launch a keratoconus screening test in Korea, Japan and China in the first quarter of 2017. [Avellino Labs] Press Release

Capricor Therapeutics Announces Plans to Expand Clinical Development Program in Duchenne Muscular Dystrophy to Evaluate Peripheral and Respiratory Muscle Function

Capricor Therapeutics, Inc. announced that it intends to expand its CAP-1002 (allogeneic cardiosphere-derived cells) clinical development program in Duchenne muscular dystrophy to encompass the skeletal muscle aspects of the disease, in addition to the cardiac complications. [Capricor Therapeutics, Inc.] Press Release

Disgraced Stem-Cell Entrepreneur under Fresh Investigation

Public prosecutors in Turin, Italy, are investigating whether disgraced stem-cell entrepreneur Davide Vannoni — convicted on criminal charges last year for administering unproven stem-cell therapies in Italy — is offering his treatments again, this time in eastern Europe. [Nature News] Editorial

The Ultimate Experiment: How Trump Will Handle Science

The long campaign for the White House is over — but incoming US president Donald Trump’s work is just starting. With just two months before his inauguration on 20 January, he and his staff are busy vetting candidates for top government jobs and clarifying the agenda for his first few months in office. [Nature News] Editorial

Embryonic Stem Cells and Fetal Tissue Research—Will Trump Intervene?

Of all the materials valued in biomedical research, embryonic stem (ES) cells and fetal tissue have gotten disproportionate attention from politicians. Because creating ES cell lines initially requires destroying a human embryo, President George W. Bush tightly restricted the use of federal funds for research on all but a few stem cell lines. President Barack Obama then made lifting those restrictions one of his first official actions after he took office in 2009. [Science Insider] Editorial

FDA

Withdrawal of Two Proposed Rules (FR Doc. No:2016-27329) Notice

Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Biological Products: Reporting of Biological Product Deviations and Human Cells, Tissues, and Cellular and Tissue-Based Deviations in Manufacturing (FR Doc. No:2016-27259) Notice

NEW ANOTHER DEATH in the ALPS: Cell Death, Inflammation and Cancer
January 10-14, 2017
Obergurgl, Austria

NEW Challenges, Solutions and Progress in Stem Cell Medicine
February 18-21, 2017
Carlsbad, United States

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NEW Research Fellow – Fat Tissue-Derived Stem Cells for Treating Metabolic Diseases (SBIC, A*STAR)

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

Associate Director – Cellular Process Development (Celgene Corporation)

Research Specialist – Tissue Regeneration Research In Vitro and In Vivo (University of Pittsburgh)

Postdoctoral Fellowship – Genetic Medicine (Weill Cornell Medical College)

Research Fellow in Pluripotent Stem Cells Self-Renewal Program and Cell Cycle (KU Leuven)

Faculty Position – Stem Cell Biology and Regenerative Medicine (Stanford University)

Research Associate – Hematology (Editas Medicine)

Postdoctoral Fellow – Novel Systems for Treatment of Type 1 Diabetes (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

Assistant Professor – Developmental Biology (Florida State University)

Postdoctoral Fellow – Pluripotent Stem Cell Technology (University of California Davis)

Postdoctoral Fellow – Oxidative Lung Injury (Temple University)

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