Cell Therapy News Volume 17.44 | Dec 5 2016

TOP STORY

Mitochondrial Replacement in Human Oocytes Carrying Pathogenic Mitochondrial DNA Mutations

Investigators report mitochondrial replacement therapies or technique outcomes in several families with common mtDNA syndromes. The mother’s oocytes were of normal quality and mutation levels correlated with those in existing children. Efficient replacement of oocyte mutant mtDNA was performed by spindle transfer, resulting in embryos containing >99% donor mtDNA. Donor mtDNA was stably maintained in embryonic stem cells derived from most embryos. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Transplanted Photoreceptor Precursors Transfer Proteins to Host Photoreceptors by a Mechanism of Cytoplasmic Fusion

The authors showed that host cells are labelled with the donor marker through cytoplasmic transfer—94±4.1% of apparently well-integrated donor cells containing both donor and host markers. They detected the occurrence of Cre-Lox recombination between donor and host photoreceptors, and they confirm the findings through FISH analysis of X and Y chromosomes in sex-discordant transplants. [Nat Commun] Full Article

Infusion with Human Bone Marrow-Derived Mesenchymal Stem Cells Improves β-Cell Function in Patients and Non-Obese Mice with Severe Diabetes

Researchers showed that infusion with bone marrow mesenchymal stem cells (MSCs) preserves β-cell function in some type 1 diabetes patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1–2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic mice with severe diabetes. [Sci Rep] Full Article

Intravenous hMSCs Ameliorate Acute Pancreatitis in Mice via Secretion of Tumor Necrosis Factor-α Stimulated Gene/Protein 6

Investigators demonstrated that intravenously (i.v.)-administered human mesenchymal stromal cells (hMSCs) remarkably promoted recovery from experimental severe acute pancreatitis (SAP) without significant engraftment of hMSCs in the damaged pancreas. Interestingly, they found that i.v.-administered hMSCs with knockdown of TSG-6 expression lost most of their anti-inflammatory effects and thus could not significantly ameliorate SAP. [Sci Rep] Full Article

Transposon-Mediated Generation of Cellular and Mouse Models of Splicing Mutations to Assess the Efficacy of snRNA-Based Therapeutics

Scientists exploited the hyperactive Sleeping Beauty transposon system to integrate human factor IX (hFIX) minigenes into genomic DNA in vitro and in vivo. They generated stable HEK293 cell lines and C57BL/6 mice harboring splicing-competent hFIX minigenes either wild type or mutated. [Mol Ther Nucleic Acids] Full Article

Efficient Generation of Orthologous Point Mutations in Pigs via CRISPR-Assisted ssODN-Mediated Homology-Directed Repair

The authors investigated single-stranded oligonucleotides (ssODN) mediated knockin by introducing two orthologous pathogenic mutations, p.E693G for Alzheimer’s disease and p.G2019S for Parkinson’s disease, into porcine APP and LRRK2 loci, respectively. Desirable homology-directed repair efficiency was achieved in porcine fetal fibroblasts by optimizing the dosage and length of ssODN templates. [Mol Ther Nucleic Acids] Full Article

Activation of Myeloid- and Endothelial Cells by CD40L Gene Therapy Supports T Cell Expansion and Migration into the Tumor Microenvironment

A novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer. Further, the CD40L mechanisms of action were elucidated in cancer models. The results demonstrated that the virus transferring TMZ-CD40L had oncolytic capacity in pancreatic cancer cells and could control tumor progression. [Gene Ther] Full Article

Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model

Scientists developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. [PLoS One] Full Article

Use of Gene-Activated Demineralized Bone Allograft in the Therapy of Ulnar Pseudarthrosis

Researchers present a clinical case of successful ulnar pseudarthrosis treatment using a gene-activated bone allograft containing vascular endothelial growth factor and bone morphogenetic protein 2 in the form of a multicystron plasmid. Demineralized bone matrix with applied recombinant plasmid DNA was grafted into the bone defect using the classical open surgical approach. [Bionanoscience] Abstract | Press Release

Transcriptional Activity of Novel ALDH1L1 Promoters in the Rat Brain following AAV Vector-Mediated Gene Transfer

Scientists generated putative promoter sequence variants of the rat ALDH1L1 gene for use in adeno-associated viral vector-mediated gene transfer, with an aim to achieve selective regulation of transgene expression in astrocytes in the rat brain. Unexpectedly, ALDH1L1 promoter variants mediated transcriptional activity exclusively in neurons in the substantia nigra pars compacta as assessed by luciferase reporter expression at three weeks postvector infusion. [Mol Ther Methods Clin Dev] Full Article

The Superior Regenerative Potential of Muscle-Derived Stem Cells for Articular Cartilage Repair Is Attributed to High Cell Survival and Chondrogenic Potential

In vivo, PP6 cells promoted superior cartilage regeneration compared with other muscle-derived cell populations. The cartilage defects in the PP6 group had significantly higher histological scores than those of the other muscle-derived cell groups, and GFP detection revealed that the transplanted PP6 cells showed superior in vivo cell survival and chondrogenic capabilities compared with the PP1 and PP3 cells. [Mol Ther Methods Clin Dev] Full Article

Non-Viral Delivery of Genome-Editing Nucleases for Gene Therapy

The authors summarize recent advances that have been made on non-viral delivery of genome-editing nucleases. In particular, they focus on non-viral delivery of Cas9/sgRNA ribonucleoproteins for genome editing. In addition, the future direction for developing non-viral delivery of programmable nucleases for genome editing is discussed. [Gene Ther] Abstract

T-Cell Programming in Pancreatic Adenocarcinoma: A Review

To harness mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of pancreatic ductal adenocarcinoma must be achieved. The outcome of T-cell programming against pathogens or cancer depends on the uptake and presentation of foreign antigens by dendritic cells and macrophages to T cells, and the expression of various co-stimulatory molecules and cytokines. [Cancer Gene Ther] Abstract

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

Spark Therapeutics and Pfizer Present Updated Preliminary Data from Hemophilia B Phase I/II Trial Suggesting Consistent and Sustained Levels of Factor IX Activity

Researchers reported the highest and most sustained levels to date of an essential blood-clotting factor IX in patients with the inherited bleeding disorder hemophilia B. After receiving a single dose of an experimental gene therapy in a clinical trial, patients with hemophilia produced near-normal levels of clotting factor IX, allowing them to stop clotting factor infusions and to pursue normal activities of daily life without disabling bleeding episodes. [Press release from Spark Therapeutics discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Novartis Presents Results from First Global Registration Trial of CTL019 in Pediatric and Young Adult Patients with R/R B-ALL

Findings from a Novartis clinical trial (ELIANA) evaluating efficacy and safety of CTL019, an investigational chimeric antigen receptor T cell (CAR T) therapy, in relapsed/refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL) will be presented during an oral session. The global Phase II study found that 82% of infused patients achieved complete remission or complete remission with incomplete blood count recovery at three months post CTL019 infusion. [Press release from Novartis discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Penn Scientists Use CRISPR for First Time to Correct Clotting in Newborn and Adult Mice

For the first time, researchers from the Perelman School of Medicine at the University of Pennsylvania have developed a dual gene therapy approach to deliver key components of a CRISPR/Cas9-mediated gene targeting system to mice to treat hemophilia B. This disorder is also called factor IX deficiency and is caused by a missing or defective clotting protein. [Press release from the Perelman School of Medicine at the University of Pennsylvania discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

CD19-Targeting CAR T-Cell Immunotherapy Yields High Responses in Treatment-Resistant CLL

In a small, early phase trial, a high percentage of patients who had exhausted most traditional treatments for chronic lymphocytic leukemia saw their tumors shrink or even disappear after an infusion of a highly targeted, experimental CAR T-cell immunotherapy developed at Seattle’s Fred Hutchinson Cancer Research Center. [Press release from Fred Hutchinson Cancer Research Center discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Agilis Biotherapeutics Announces Orphan Designation Approval in Europe for the Treatment of AADC Deficiency

Agilis Biotherapeutics announced that the European Commission has granted Orphan Medicinal Product designation in the European Union to the company’s gene therapy product candidate, AGIL-AADC. [Agilis Biotherapeutics] Press Release

Audentes Therapeutics Announces Initiation of Large-Scale cGMP Production at its Gene Therapy Manufacturing Facility

Audentes Therapeutics, Inc. announced it has successfully initiated large-scale cGMP (current Good Manufacturing Practice) production runs in its new, state-of-the-art manufacturing facility. [Audentes Therapeutics, Inc.] Press Release

Calimmune Expands Lentiviral Gene Therapy Pipeline through License of Sickle Cell Disease Therapeutic Candidate

Calimmune, Inc. announced a license agreement with Cincinnati Children’s Hospital Medical Center to develop and commercialize gene therapies combining Calimmune’s Select+^™ technology with Cincinnati Children’s proprietary gene therapy construct for the treatment of patients with sickle cell disease and beta thalassemia. [Calimmune, Inc.] Press Release

Salk Institute Names Ted Waitt Board Chairman

Ted Waitt, chairman of the Waitt Foundation and cofounder of Gateway, Inc., a pioneer in the direct marketing of personal computers, has been named chairman of the Salk Institute for Biological Studies’ Board of Trustees. He assumes his new role immediately. [Salk Institute for Biological Studies] Press Release

Sangamo’s Genome Editing Program for Hemoglobinopathies to Transfer to Biogen’s Spin-Off Bioverativ

Sangamo BioSciences, Inc. announced that its collaborative zinc finger nuclease-mediated genome editing program for hemoglobinopathies will transfer to Bioverativ. [Sangamo BioSciences, Inc.] Press Release

Sorrento’s TNK Therapeutics Provides Progress Update for its Anti-CD38 and CD123 CAR-T Programs for Treatment of Hematological Malignancies

TNK Therapeutics, Inc. has provided an update on its lead chimeric antigen receptor expressing T cells (CAR-T) programs for the treatment of hematological malignancies. Adoptive immunotherapy utilizing CAR-T cells represents a promising new paradigm in the treatment of cancer. [TNK Therapeutics, Inc.] Press Release

Allen Institute for Cell Science Releases Gene Edited Human Stem Cell Lines

The Allen Institute for Cell Science has released the Allen Cell Collection: the first publicly available collection of gene edited, fluorescently tagged human induced pluripotent stem cells that target key cellular structures with unprecedented clarity. Distributed through the Coriell Institute for Medical Research, these powerful tools are a crucial first step toward visualizing the dynamic organization of cells to better understand what makes human cells healthy and what goes wrong in disease. [The Allen Institute for Cell Science] Press Release

Genetic Rx Panel on Gene Therapy to Feature Renova Therapeutics CEO and Co-Founder

Renova™ Therapeutics announced that the company’s CEO and co-founder, Jack W. Reich, Ph.D., will be speaking on a panel about gene therapy at Genetic Rx, a networking conference of the Boston Biotech conferences series. [Renova™ Therapeutics] Press Release

Maryland Congressman in Running to Head NIH?

Representative Andy Harris (R–MD), an anesthesiologist who has shown a keen interest in the National Institutes of Health (NIH) while in Congress, has put his hat in the ring for NIH director in the incoming administration of President-elect Donald Trump, he told ScienceInsider. Harris says he knows that some biomedical scientists would view him as a controversial choice, but argues that his blend of research and political experience would make him a good advocate for addressing NIH’s flaws and for growing the agency’s budget in a time of fiscal restraint. [ScienceInsider] Editorial

FDA

Agency Information Collection Activities: Proposed Collection; Comment Request; Guidance for Industry on Expedited Programs for Serious Conditions-Drugs and Biologics (FR Doc. No:2016-28732) Notice

Determination of Regulatory Review Period for Purposes of Patent Extension; IXINITY (FR Doc. No:2016-28653) Notice

Determination of Regulatory Review Period for Purposes of Patent Extension; TRESIBA (FR Doc. No:2016-28939) Notice

NEW Gordon Research Conference: Stem Cells & Cancer
February 12-17, 2017
Barga, Italy

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

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

NEW Postdoctoral Fellowship – Stem Cell and Red Cell Biology (Lund University)

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

NEW Postdoctoral Fellow – Statistical Computing in Cancer Research and Personalized Medicine (European Molecular Biology Laboratory)

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

Division Head – Cell Labeling and Sensing (Helmholtz Zentrum München)

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)

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)

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.