Cell Therapy News Volume 18.01 | Jan 16 2017

TOP STORY

Human AML-iPSCs Reacquire Leukemic Properties after Differentiation and Model Clonal Variation of Disease

The authors generated induced pluripotent stem cells (iPSCs) from acute myeloid leukemia (AML) patient samples harboring MLL rearrangements and found that they retained leukemic mutations but reset leukemic DNA methylation/gene expression patterns. AML-iPSCs lacked leukemic potential, but when differentiated into hematopoietic cells, they reacquired the ability to give rise to leukemia in vivo and reestablished leukemic DNA methylation/gene expression patterns, including an aberrant MLL signature. [Cell Stem Cell] Abstract

(Ranked by impact factor of the journal)

Transfer of Minimally Manipulated CMV-Specific T Cells from Stem Cell or Third-Party Donors to Treat CMV Infection after AlloHSCT

Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The scientists assessed prospectively safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a Phase I/IIa trial. [Leukemia] Abstract

Haploidentical Transplantation with Post-Infusion Cyclophosphamide in Advanced Hodgkin Lymphoma

Researchers investigated the use of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of advanced Hodgkin lymphoma (HL). Sixty-two consecutive HL patients underwent haplo-HSCT. Unmanipulated stem cells and post-transplant cyclophosphamide were given to all patients as GVHD prophylaxis. [Leukemia] Abstract

Quantitative Stability of Hematopoietic Stem and Progenitor Cell Clonal Output in Transplanted Rhesus Macaques

Investigators documented very stable multipotent long-term hematopoietic clonal output of monocytes, granulocytes, B cells and T cells from a polyclonal pool of hematopoietic stem and progenitor cells in four macaques followed for up to 49 months post-transplantation. A broad range of clonal behaviors characterized by contribution level and biases towards certain cell types were extremely stable over time. [Blood] Abstract

iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice

By transplanting mouse induced pluripotent stem cell-derived retinal tissue (miPSC retina) in the end-stage retinal-degeneration model (rd1), scientists visualized the direct contact between host bipolar cell terminals and the presynaptic terminal of graft photoreceptors by gene labeling, showed light-responsive behaviors in transplanted rd1 mice, and recorded responses from the host retina with transplants by ex vivo micro-electroretinography and ganglion cell recordings using a multiple-electrode array system. [Stem Cell Reports] Full Article | Press Release 1 | Press Release 2

HIF-2α and Oct4 Have Synergistic Effects on Survival and Myocardial Repair of Very Small Embryonic-Like Mesenchymal Stem Cells in Infarcted Hearts

Under hypoxic condition, very small embryonic-like mesenchymal stem cells (vselMSCs) exhibited stronger survival, proliferation and differentiation than unpurified MSC. Transplantation of vselMSCs caused greater improvement in cardiac function and heart remodeling in the infarcted rats. [Cell Death Dis] Full Article

Efficient Generation of HPSC-Derived Midbrain Dopaminergic Neurons in a Fully Defined, Scalable, 3D Biomaterial Platform

Scientists used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing dopaminergic (mDA) neurons after 25 days of differentiation. Importantly, mDA neurons generated in 3D exhibited a 30-fold increase in viability upon implantation into rat striatum compared to neurons generated on 2D, consistent with the elevated expression of survival markers FOXA2 and EN1 in 3D. [Sci Rep] Full Article

Intraarterial Route Increases the Risk of Cerebral Lesions after Mesenchymal Cell Administration in Animal Model of Ischemia

Researchers investigated whether mesenchymal stem cells (MSCs) reached the brain following intraarterial or intravenous administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging cell tracking, transmission electron microscopy and immunohistological analysis. [Sci Rep] Full Article

Adipose Stem Cell-Derived Nanovesicles Inhibit Emphysema Primarily via an FGF2-Dependent Pathway

Recently, nanovesicles that overcome the disadvantages of natural exosomes have been generated artificially from cells. Investigators generated artificial nanovesicles from adipose-derived stem cells using sequential penetration through polycarbonate membranes. [Exp Mol Med] Full Article

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

The authors hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require tripeptidyl peptidase-1 (TPP1) for normal lysosomal function. To test this hypothesis, dogs treated with cerebrospinal fluid administration of AAV-TPP1 were evaluated for development of non-neuronal pathology. [Gene Ther] Full Article

Telomerase Specific Oncolytic Adenovirus Expressing TRAIL Suppresses Peritoneal Dissemination of Gastric Cancer

Scientists used an oncolytic adenovirus vector (Ad/TRAIL-E1) that expresses both the TRAIL and E1A genes under the control of a tumor-specific promoter. They evaluated the anti-tumor effect of Ad/TRAIL-E1 on gastric cancer cells in vitro, as well as in vivo in a xenograft peritoneal carcinomatosis mouse model. [Gene Ther] Abstract

Therapeutic Vaccination Based on Side Population Cells Transduced by the Granulocyte–Macrophage Colony-Stimulating Factor Gene Elicits Potent Antitumor Immunity

Researchers showed that gene-transduced tumor cell vaccine therapy targeting cancer stem cells (CSCs) substantially suppressed tumor development in syngeneic immunocompetent mice recapitulating normal immune systems. CSCs were isolated as side population cells from 4T1 murine breast carcinoma cell line and transduced with granulocyte–macrophage colony-stimulating factor gene delivered by non-transmissible Sendai virus. [Cancer Gene Ther] Abstract

Adoptive Cellular Immunotherapy for Virus-Associated Cancers: A New Paradigm in Personalized Medicine

While autologous T cell therapies have provided promising results, development of ‘off-the-shelf’ third-party allogeneic virus-specific T cell therapies have emerged as powerful tools to treat many of the virus-associated diseases. It is anticipated that adoptive T cell therapy in combination with newly emerging immune checkpoint inhibitors and therapeutic vaccines will provide opportunities to successfully treat advanced metastatic virus-associated cancers which are currently not amenable to standard therapeutic strategies. [Immunol Cell Biol] Abstract

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Kite Pharma and Fosun Pharma Establish Joint Venture in China to Develop and Commercialize Autologous T-Cell Therapies to Treat Cancer

Kite Pharma and Shanghai Fosun Pharmaceutical Co., Ltd. announced a joint venture, Fosun Pharma Kite Biotechnology Co., Ltd. to develop, manufacture and commercialize axicabtagene ciloleucel in China with the option to include additional products, including two T cell receptor product candidates from Kite. Axicabtagene ciloleucel, Kite’s lead product candidate, is an investigational chimeric antigen receptor T-cell therapy under development for the treatment of B-cell lymphomas and leukemias. [Kite Pharma] Press Release

Amgen and Immatics Enter Strategic Collaboration to Develop Novel Bispecific Cancer Immunotherapies

Amgen and Immatics Biotechnologies GmbH announced a research collaboration and exclusive license agreement to develop next-generation, T-cell engaging bispecific immunotherapies targeting multiple cancers. The collaboration will combine Immatics’ world-leading XPRESIDENT^® target discovery and T-cell receptor capabilities with Amgen’s validated Bispecific T-cell Engager technology with the aim of creating novel oncology drugs. Amgen will be responsible for the clinical development, manufacturing and commercialization worldwide. [Immatics Biotechnologies GmbH] Press Release

Maverick Therapeutics and Takeda Announce Five-Year Collaboration to Advance T-Cell Engagement Therapies

Maverick Therapeutics Inc. and Takeda Pharmaceutical Company Limited announced that they have entered a collaboration to develop Maverick’s T-cell engagement platform created specifically to improve the utility of T-cell redirection therapy for the treatment of cancer. The $125 million of funding includes an upfront option, equity and research and development funding payments, and provides Takeda the exclusive right to purchase Maverick after five years for an undisclosed sum. [Takeda Pharmaceutical Company Limited] Press Release

ZIOPHARM and Intrexon Announce Cooperative Research and Development Agreement with the National Cancer Institute Utilizing Sleeping Beauty System to Generate T Cells Targeting Neoantigens

ZIOPHARM Oncology, Inc. and Intrexon Corporation announced the signing of a Cooperative Research and Development Agreement with the National Cancer Institute for the development of adoptive cell transfer-based immunotherapies genetically modified using the Sleeping Beauty transposon/transposase system to express T-cell receptors for the treatment of solid tumors. [ZIOPHARM Oncology, Inc.] Press Release

European Commission Ratifies Positive CHMP Opinion for the Renewal of Translarna^™ Marketing Authorization for the Treatment of Nonsense Mutation Duchenne Muscular Dystrophy

PTC Therapeutics, Inc. announced that it received notification from the European Commission of its adoption of a positive decision granting annual renewal of the conditional marketing authorization for Translarna^™. The positive decision is based on the recent renewal recommendation by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency. [PTC Therapeutics, Inc.] Press Release

Sangamo Therapeutics Receives Orphan Drug Designation from the FDA for SB-318 Genome Editing Treatment for MPS I

Sangamo Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to SB-318, a genome editing product candidate for the treatment of Mucopolysaccharidosis Type I (MPS I), a rare lysosomal storage disorder. MPS I is caused by mutations in the gene encoding the alpha-L-iduronidase (IDUA) enzyme. Using Sangamo’s zinc finger nuclease genome editing technology, SB-318 is designed as a single treatment strategy intended to provide stable, continuous production of the IDUA enzyme for the lifetime of the patient. [Sangamo Therapeutics, Inc.] Press Release

ViraCyte Granted U.S. FDA Fast Track Designation for Viralym-C

ViraCyte, LLC announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Viralym-C, ViraCyte’s T cell immunotherapy product designed to treat refractory cytomegalovirus infections in patients following a stem cell transplant. [ViraCyte, LLC (PR Newswire Association LLC.)] Press Release

Provia Laboratories Posts Record Year in Enrollments for Its Store-a-Tooth^™ Dental Stem Cell Technology and Gives 2017 Guidance

Grace Century’s bio banking project, Provia Laboratories, LLC has reported another yearly record in enrollments for their Store-a-tooth^™ cryogenic storage service of dental stem cells, as well as securing facilities for European expansion. Provia saw a +20% increase in enrollments for year over year. This is proof of the demand resonating from families’ awareness of the possible future uses of stem cells and the research on emerging therapies being reported. [Grace Century] Press Release

Surprising Contenders Emerge for Trump’s NIH Chief

Could US president-elect Donald Trump be close to choosing a leader for the National Institutes of Health (NIH)? Current NIH chief Francis Collins and Representative Andy Harris (Republican, Maryland), both front-runners for job, met separately with Trump, as did billionaire surgeon Patrick Soon-Shiong. Several people familiar with the Collins and Harris meetings described them as job interviews. [Nature Breaking News] Editorial

European Commission Clears Up Questions on Orphan Drug Regulation

Following a public consultation in November 2015, the European Commission has released a new communication intended to clarify some lingering questions about the EU’s Orphan Regulation. The consultation sought to address five issues that have arisen since the Orphan Regulation came into effect in January 2000. [Regulatory Affairs Professionals Society] Editorial

Gates Foundation Research Can’t Be Published in Top Journals

One of the world’s most influential global health charities says that the research it funds cannot currently be published in several leading journals, because the journals do not comply with its open-access policy. [Nature News] Editorial

FDA

Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an Abbreviated New Drug Application; Draft Guidance for Industry; Availability (FR Doc. No:2017-00795) Notice

Suggestions, Recommendations, and Comments for Topics That May Be Considered by the Food and Drug Administration Combination Product Policy Council; Establishment of a Docket (FR Doc. No:2017-00646) Notice

Factors To Consider When Making Benefit-Risk Determinations for Medical Device Investigational Device Exemptions; Guidance for Investigational Device Exemption Sponsors, Sponsor-Investigators, and Food and Drug Administration Staff; Availability (FR Doc. No:2017-00604) Notice

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

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

NEW Postdoctoral Fellow – Various Projects (University of Oklahoma)

NEW Scientist – Regulatory Support (Cook MyoSite, Inc.)

NEW Scientist – Regulatory Affairs (Cook MyoSite, Inc.)

Senior Scientist – Engineered T Cells Used in Adoptive Cell Therapies (Immatics)

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)

Independent Research Group Leaders – Stem Cell Science (University of Cambridge)

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

Pioneer/Division Head – Human Organoids (Helmholtz Zentrum München)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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)

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