Cell Therapy News Volume 18.11 | Apr 3 2017

TOP STORY

Sphingosine-1-Phosphate Prevents Egress of Hematopoietic Stem Cells from Liver to Reduce Fibrosis

Purified hematopoietic stem cells (HSC) were repeatedly infused into mice undergoing fibrotic liver injury. Chronic liver injury was induced in BoyJ mice by injection of carbon tetrachloride or placement on methionine/choline deficient diets. Some mice were irradiated and given transplants of bone marrow cells from C57BL6 mice, with or without the S1P antagonist FTY720; the authors then studied HSC mobilization and localization. [Gastroenterology] Full Article

(Ranked by impact factor of the journal)

Left Ventricular Dysfunction Switches Mesenchymal Stromal Cells toward an Inflammatory Phenotype and Impairs Their Reparative Properties via Toll-Like Receptor-4

Investigators isolated mesenchymal stromal cells (MSCs) from cardiac (c) and subcutaneous (sc) fat tissues of mice with left ventricular dysfunction (LVD), 28 days after myocardial infarction (MI), or sham operation. To evaluate the effect of LVD on MSCs, they characterized cMSCs and scMSCs in vitro. Subsequently, they injected MSCs or saline into the infarcted myocardium of mice and evaluated left ventricular remodeling, and function, 28 days after MI. [Circulation] Abstract

5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency

Scientists report sustained expression at 2.0-2.5% of the target level from years one to five in patients without any additional recombinant adeno-associated virus serotype-1 alpha-1 antitrypsin vector administration. In addition, they observed partial correction of disease-associated neutrophil defects, including neutrophil elastase inhibition, markers of degranulation and membrane-bound anti-neutrophil antibodies. [Mol Ther] Full Article

Cell-Based Therapy Using miR-302-367 Expressing Cells Represses Glioblastoma Growth

MicroRNA (miR)-302-367 cell-to-cell transfer resulted in the inhibition of its targets such as CXCR4/SDF1, SHH, cyclin D, cyclin A and E2F1. Orthotopic xenograft of miR-302-367-expressing cells together with glioblastoma stem-like cells efficiently altered the tumor development in mice brain. [Cell Death Dis] Full Article

Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue

Researchers describe a scalable, porous large-format engineered cardiac tissue composed of human induced pluripotent stem cells derived multiple lineage cardiac cells with varied 3D geometries and cell densities developed towards the goal of scale-up for large animal pre-clinical studies. The 6M-mesh-engineered cardiac tissue implanted onto one week post-infarct immune tolerant rat hearts engrafted, displayed evidence for host vascular coupling, and recovered myocardial structure and function with reduced scar area. [Sci Rep] Full Article

Tubular Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells Generate Pulse Pressure In Vivo

Human induced pluripotent stem cells induced to cardiomyocytes in suspension were cultured on temperature-responsive dishes to fabricate cardiac cell sheets. Two pairs of triple-layered sheets were transplanted to wrap around the inferior vena cava (IVC) of nude rats. At four weeks after transplantation, inner pressure changes in the IVC were synchronized with electrical activations of the graft. [Sci Rep] Full Article

Multiple Myeloma Patients in Long-Term Complete Response after Autologous Stem Cell Transplantation Express a Particular Immune Signature with Potential Prognostic Implication

To evaluate whether long-term complete response (LTCR) is associated with a particular immune signature, peripheral blood samples from 13 LTCR-multiple myeloma after autologous stem cell transplantation and healthy patients were analyzed. Subpopulations of T-cells, B-cells and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry. [Bone Marrow Transplant] Abstract

A Preclinical Evaluation of Alternative Site for Islet Allotransplantation

Scientists aimed to compare the bone marrow cavity (BMC) with the liver as an islet allotransplantation site in diabetic monkeys. Diabetes was induced in Rhesus monkeys using streptozocin, and the monkeys were then divided into the following three groups: Group 1 (islets transplanted in the liver with immunosuppressant), Group 2 (islets transplanted in the tibial BMC), and Group 3 (islets transplanted in the tibial BMC with immunosuppressant). [PLoS One] Full Article

Stiffness of Protease Sensitive and Cell Adhesive PEG Hydrogels Promotes Neovascularization In Vivo

The allyloxycarbonyl functionality group competes with acrylates during photopolymerization to alter the crosslink network structure and reduce the poly(ethylene glycol) hydrogel’s stiffness. Hydrogels that incorporated or lacked this group were implanted subcutaneously in rats to investigate the role of stiffness on host tissue interactions. Changes in tissue integration were quantified after four weeks via the hydrogel area replaced by native tissue, yielding 0.136 for softer vs. 0.062 for stiffer hydrogels. [Ann Biomed Eng] Abstract

Therapeutic Progenitor Cell Application for Tissue Regeneration: Analyzing the Impact of Toll-Like Receptor Signaling on c-Kit⁺ Cell Migration following Ischemia-Reperfusion Injury In Vivo

It has not been described conclusively whether migration of therapeutically applied progenitor cells following an ischemia-reperfusion (IR) event depends on Toll-like-receptor (TLR)-signaling. In vivo migratory capacity murine c-kit⁺ cells following IR injury was quantified by intravital fluorescence microscopy, utilizing the mouse cremaster muscle model and analyzing early and late c-kit⁺ cell interaction with the local endothelium. [Microvasc Res] Abstract

Chimeric Antigen Receptors (CARs)–a Cell and Gene Therapy Perspective

CD19 CAR therapy is predicated on advances in genetic engineering, T cell biology, tumor immunology, synthetic biology, target identification, cell manufacturing sciences and regulatory compliance, central tenets of CAR therapy. The authors review two of these foundations—the genetic engineering approaches and cell types to which to apply them. [Mol Ther] Abstract

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

Sangamo Therapeutics Announces Presentation of New Data Demonstrating Significant Reduction of Tau Expression Using Proprietary ZFP Gene Regulation Technology

Sangamo Therapeutics, Inc. announced the presentation of new human in vitro and animal model data demonstrating significant reduction of tau mRNA and tau protein expression using the company’s zinc finger protein transcription factor-mediated gene regulation technology. These results are the first evidence of a tau lowering agent demonstrating efficacy on neuritic dystrophy in an amyloid mouse model of Alzheimer’s disease. [Press release from Sangamo Therapeutics, Inc. discussing research presented at 13^th International Conference on Alzheimer’s & Parkinson’s Diseases, Vienna] Press Release

OncoSec Presents Preclinical Data Demonstrating Improved Systemic Anti-Tumor Response following Modifications to IL-12 Gene Delivery Therapy

OncoSec Medical Incorporated presented a poster titled “Intratumoral Delivery of a P2A-linked Bicistronic IL-12 Construct Leads to High Intratumoral Expression and Systemic Anti-tumor Response” (Abstract ID # 1614). The poster included preclinical data demonstrating the latest developments of OncoSec’s gene delivery platform in a murine melanoma model. [Press release from OncoSec Medical Incorporated discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting, Washington, D.C.] Press Release

Kite Presents Ongoing Response Rate in Plenary Session from Its Pivotal CAR-T Trial of Axicabtagene Ciloleucel in Patients with Aggressive Non-Hodgkin Lymphoma

Kite Pharma, Inc. announced two plenary presentations of positive data from the primary analysis of ZUMA-1 for its lead CAR-T candidate, axicabtagene ciloleucel, in patients with refractory aggressive B-cell non-Hodgkin lymphoma (NHL). The study met the primary endpoint of objective response rate recorded after a single infusion of axicabtagene ciloleucel, with 82 percent. These results demonstrated the treatment effect of axicabtagene ciloleucel in diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and transformed follicular lymphoma, which are types of aggressive NHL. [Press release from Kite Pharma, Inc. discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting, Washington, D.C.] Press Release

STEMCELL Technologies to Launch CloneR^™ to Facilitate Genome Editing of Human Pluripotent Stem Cells

STEMCELL Technologies announced the development of CloneR^™, a novel medium formulation to aid researchers in their ability to successfully genome edit human pluripotent stem cells. This supplement represents a dramatic improvement over existing technologies. [STEMCELL Technologies] Press Release

Aldevron Licenses Minicircle Technology to Support Collaboration with Myeloma Crowd and the Development of Multiple Myeloma Treatments

Aldevron, along with the Myeloma Crowd will collaborate to support research toward the advancement of treatments and a cure for multiple myeloma. Under the collaboration, Aldevron licensed technology developed by Mark Kay, Dennis Farrey Family Professor in Pediatrics and Professor of Genetics at Stanford University, to manufacture minicircle DNA for non-profit organizations. Aldevron will be producing minicircle DNA products to support research sponsored by the Myeloma Crowd Research Initiative to develop Chimeric Antigen Receptor T-Cells for the treatment of hematologic malignancies including multiple myeloma. [Aldevron] Press Release

Kiadis Pharma Announces Positive Regulatory Update on ATIR101^™ and ATIR201^™

Kiadis Pharma N.V. announces that it has obtained regulatory approval from the national authority in Belgium to start its randomized, controlled, transatlantic Phase III clinical trial with ATIR101^™ for acute leukemia in Belgium. [Kiadis Pharma N.V.] Press Release

Audentes Therapeutics Announces FDA Clearance of Investigational New Drug Application for AT132 to Treat X-Linked Myotubular Myopathy

Audentes Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for AT132, the company’s gene therapy product candidate to treat X-Linked Myotubular Myopathy. The IND is now active and Audentes plans to initiate ASPIRO, the multicenter, multinational, open-label, ascending dose Phase I/II clinical study of AT132. [Audentes Therapeutics, Inc.] Press Release

RepliCel’s Successful RCT-01 Tendon Repair Clinical Trial Shows Signs of Healing Chronic Tendon Problems

RepliCel Life Sciences Inc. reported compelling safety and clinical data from its Phase I/II tendon repair study investigating the use of RepliCel’s type 1 collagen-expressing, hair follicle-derived fibroblasts (RCT-01) as a treatment for Achilles tendinosis. [RepliCel Life Sciences Inc.] Press Release

Sorrento Therapeutics Anti-CEA CAR-T Demonstrates Promising Clinical Activity and Safety in Phase Ib Clinical Trial

Sorrento Therapeutics, Inc. announced the results from the Hepatic ImmunoTherapy for Metastases-Selective Internal Radiation Therapy, a Phase Ib single arm trial testing its anti-CEA CAR-T administered regionally by hepatic artery infusion followed by selective internal radiation therapy in heavily pre-treated patients with CEA positive liver metastases. [Sorrento Therapeutics, Inc.] Press Release

Novartis Announces First CAR-T Cell Therapy BLA for Pediatric and Young Adult Patients with R/R B-Cell ALL Granted FDA Priority Review

Novartis announced that the US Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) filing and granted priority review for CTL019, an investigational chimeric antigen receptor T cell (CAR-T) therapy, in relapsed and refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). [Novartis] Press Release

Kite Completes Submission of U.S. Biologics License Application (BLA) for Axicabtagene Ciloleucel as the First CAR-T Therapy for the Treatment of Patients with Aggressive Non-Hodgkin Lymphoma (NHL)

Kite Pharma, Inc. announced that it has completed the rolling submission with the U.S. Food and Drug Administration of the BLA for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory aggressive NHL who are ineligible for autologous stem cell transplant. [Kite Pharma, Inc.] Press Release

2017 Canada Gairdner Awards Recognize Basic and Transformative Research in Canada and Internationally

The Gairdner Foundation announced the 2017 Canada Gairdner Award laureates, recognizing some of the most significant medical discoveries from around the world. The awards carry an honorarium of $100,000 for each of the seven awards and will be presented at a gala in Toronto on October 26, 2017. [Gairdner Foundation] Press Release

Brazilian Scientists Reeling as Federal Funds Slashed by Nearly Half

Brazilian scientists have been left horrified by a 44% slash to the federal science budget, announced by the country’s government. This will leave the Ministry of Science, Technology, Innovations and Communications with its lowest budget in at least 12 years at just 2.8 billion reais, equivalent to US$898 million — a 2.2 billion reais cut from the 5 billion reais of funding that the government had originally proposed for 2017. [Nature News] Editorial

Genetic Details of Controversial ‘Three-Parent Baby’ Revealed

When a US fertility clinic revealed last year that it had created a baby boy using a controversial technique that mixes DNA from three people, scientists were quick to raise the alarm. Some objected on ethical grounds, and others questioned the scientific claims made by the clinic’s leader, physician John Zhang. [Nature News] Editorial

Few U.S. Animal Inspections Are Being Posted

The Donald Trump administration appears to have reversed its decision to remove from public sight the results of past government inspections of animal research facilities. But getting hold of new inspection reports is proving to be another matter. An animal welfare researcher has found that only four reports have been posted during the first quarter of 2017. [ScienceInsider] Editorial

FDA

Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Human Cells, Tissues, and Cellular and Tissue-Based Products: Establishment Registration and Listing; Eligibility Determination for Donors; and Current Good Tissue Practice (FR Doc. No:2017-06398) Notice

Delayed Graft Function in Kidney Transplantation: Developing Drugs for Prevention; Draft Guidance for Industry; Availability (FR Doc. No:2017-05818) Notice

Identification and Characterization of the Infectious Disease Risks of Human Cells, Tissues, and Cellular and Tissue-Based Products; Public Workshop; Correction (FR Doc. No:2017-05417) Notice

NEW The Bioprocessing Summit
August 21-25, 2017
Boston, United States

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

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

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

Research Associate – Stem Cell Depletion for the Preservation of Regenerative Fitness (University of Bristol)

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

Postdoctoral Fellow – Gene and Stem Cell Therapy Program (Centenary Institute)

Postdoctoral Research Fellow – Preclinical Models of Cancer Immunotherapy (Providence Cancer Center)

Principle Investigator and Postdoctoral Positions – Various Projects (Guangzhou Women and Children’s Medical Center)

BIH Chair for Cell and Gene Therapy and Coordinator of the Advanced Therapies Program (Berlin Institute of Health)

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

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

Medical Director – Clinical Research Physician (Celgene Corporation)

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)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Cell Therapy News? Click here to submit!

Comments or suggestions? Submit your feedback here.