Cell Therapy News Volume 14.20 | May 27 2013

Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors
In tumor-bearing mice, researchers found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40. They showed that intratumoral coinjection of anti-CTLA-4 and anti-OX40 together with CpG depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed with low doses of antibodies in a single tumor, generated a systemic antitumor immune response that eradicated disseminated disease in mice. [J Clin Invest] Full Article | Press Release

Outcome of Patients with Hemoglobinopathies Given Either Cord Blood or Bone Marrow Transplantation from an HLA-Identical Sibling
Investigators analyzed the outcomes of 485 patients with thalassemia major or sickle cell disease receiving HLA-identical sibling cord blood transplantation or bone marrow transplantation. [Blood] Abstract

Brief Demethylation Step Allows the Conversion of Adult Human Skin Fibroblasts into Insulin-Secreting Cells
Adult human skin fibroblasts were exposed for 18 hours to the DNA methyltransferase inhibitor 5-azacytidine, followed by a three-step protocol for the induction of endocrine pancreatic differentiation that lasted 36 days. At the end of this treatment, 35 ± 8.9% fibroblasts became pancreatic converted cells that acquired an epithelial morphology, produced insulin, and then released the hormone in response to a physiological glucose challenge in vitro. Furthermore, pancreatic converted cells were able to protect recipient mice against streptozotocin-induced diabetes, restoring a physiological response to glucose tolerance tests. [Proc Natl Acad Sci USA] Abstract

PHD2 Silencing Enhances the Survival and Paracrine Function of Transplanted Adipose-Derived Stem Cells in Infarcted Myocardium
Investigators studied if and how prolyl hydroxylase domain protein 2 (PHD2) silencing in human adipose-derived stem cells enhances their cardioprotective effects after transplantation into infarcted hearts. [Circ Res] Abstract

Parallel Assessment of Globin Lentiviral Transfer in Induced Pluripotent Stem Cells and Adult Hematopoietic Stem Cells Derived from the Same Transplanted β-Thalassemia Patient
A patient with β^β/β⁰-thalassemia major was converted to transfusion-independence 4.5 years ago by lentiviral gene transfer in hematopoietic stem cells while showing a myeloid-biased cell clone. To investigate both vector integration skewing and the potential use of induced pluripotent stem cells (iPSCs) for the treatment of thalassemia, researchers derived iPSCs from the thalassemia gene therapy patient and compared iPSC-derived hematopoietic cells to their natural isogenic somatic counterparts. [Stem Cells] Abstract

Discarded Human Kidneys as a Source of ECM Scaffold for Kidney Regeneration Technologies
Researchers previously showed that decellularization of porcine kidneys yields renal extracellular matrix (ECM) scaffolds that maintain their basic components, support cell growth and welfare in vitro and in vivo, and show an intact vasculature that, when such scaffolds are implanted in vivo, is able to sustain physiological blood pressure. Here they tested if the same strategy can be applied to discarded human kidneys in order to obtain human renal ECM scaffolds. [Biomaterials] Abstract | Press Release

Genetically Engineered Human Islets Protected from CD8-Mediated Autoimmune Destruction In Vivo
Scientists engineered human β cells to express herpesvirus-encoded immune-evasion proteins, “immunevasins”. The capacity of immunevasins to protect β cells from autoreactive T-cell killing was evaluated in vitro and in vivo in humanized mice. Coimplantation of these genetically modified pseudoislets with β-cell-specific cytotoxic T cells into immunodeficient mice achieves preserved human insulin production and C-peptide secretion. [Mol Ther] Abstract

Therapeutic Response in Feline Sandhoff Disease Despite Immunity to Intracranial Gene Therapy
Salutary responses to adeno-associated viral (AAV) gene therapy have been reported in the mouse model of Sandhoff disease, a neurodegenerative lysosomal storage disease caused by deficiency of β-N-acetylhexosaminidase. Because a pronounced humoral immune response to both the AAV1 vectors and human hexosaminidase was documented, feline cDNAs for the hexosaminidase α- and β-subunits were cloned into AAVrh8 vectors. [Mol Ther] Abstract

Angiopep-Conjugated Nanoparticles for Targeted Long-Term Gene Therapy of Parkinson’s Disease
Researchers prepared an angiopep-conjugated dendrigraft poly-L-lysine-based gene delivery system and evaluated the neuroprotective effects in the rotenone-induced chronic model of Parkinson’s disease. [Pharm Res] Abstract

Adipose Tissue-Derived Multipotent Stromal Cells Have a Higher Immunomodulatory Capacity Than Their Bone Marrow-Derived Counterparts
Investigators systematically compared the immunomodulatory capacities of bone marrow-derived multipotent stromal cells (BM-MSCs) and adipose tissue-derived multipotent stromal cells (AT-MSCs) derived from age-matched donors. They concluded that the immunomodulatory capacities of BM-MSCs and AT-MSCs are similar, but that differences in cytokine secretion cause AT-MSCs to have more potent immunomodulatory effects than BM-MSCs. [Stem Cells Transl Med] Abstract | Press Release

Encouraging Data from Stem Cell Trial in Stroke Patients as Plans for Phase II Progress
Updated interim data from the PISCES trial, which has seen the brains of ischemic stroke patients injected with neural stem cells to test the safety and tolerability of the treatment, was presented. Researchers reported that data from the first nine patients treated has shown no cell-related or immunological adverse effects. They added that most patients had experienced sustained modest reductions in neurological impairment compared to their pre-treatment baseline performance, accompanied by improvement in abilities to undertake day to day tasks. [Press release from the University of Glasgow discussing research presented at the 22^nd European Stroke Conference, London] Press Release

Ceregene Reports Additional Efficacy Data from Parkinson’s Disease Phase IIb Study
CERE-120 is a gene therapy product designed to deliver the neurotrophic factor neurturin, for Parkinson’s disease. This exploratory analysis identified a more robust response to CERE-120 in Parkinson’s patients diagnosed within 5 years prior to treatment relative to those diagnosed 10 years or more (p less than .005), as measured by change from baseline on the Unified Parkinson’s Disease Rating Scale or motor-off, the primary endpoint for this study. [Press release from Ceregene, Inc. discussing research presented at the 16^th Annual Meeting of the American Society of Gene and Cellular Therapy, Salt Lake City] Press Release

Neuralstem ALS Trial Principal Investigator, Dr. Eva Feldman, Presented Phase I Data
Neuralstem, Inc. reported that Eva Feldman, MD, PhD, principal investigator, presented updated Phase I data from its spinal cord-derived human neural stem cell (NSI-566) trial in the treatment of amyotrophic lateral sclerosis. [Press release from Neuralstem, Inc. discussing research presented at the Neuro Diabetes Medical Symposium, Romania] Press Release

Italian Parliament Orders Clinical Trial of Controversial Stem Cell Treatment
A controversial Italian stem cell therapy that scientists say is unproven will undergo its first solid scientific test. The Italian Senate voted in favor of a new bill that sets aside €3 million for a clinical trial of the treatment, devised by the Stamina Foundation in Turin. Meanwhile, the foundation can continue treating 12 patients at a hospital in Brescia who are already undergoing the disputed therapy. [Italian Senate, Italy] Press Release

Stem Cell Lobbying Group Closing Its Doors After 12 Years
In a sign of how much the controversy over human embryonic stem cells (hESCs) has waned, the most prominent lobbying group for hESC research announced that it is folding after 12 years. The Coalition for the Advancement of Medical Research will transfer its work to another group that focuses on moving hESC research into the clinic. [Coalition for the Advancement of Medical Research, United States] Press Release

Cell Investigating Breakthrough Stem Cell Paper
Eight years after South Korean stem cell scientists were exposed in one of the biggest scientific frauds ever, a paper claiming to have achieved work they faked is itself under investigation. A group led by Shoukhrat Mitalipov of the Oregon National Primate Research Center in Beaverton reported in Cell that it had used cloning to make personalized human embryonic stem cells. [ScienceInsider] Press Release

Russian Academy Awaits New Head
Awaiting the first new Russian Academy of Sciences president in more than two decades, Russian scientists hope that the leadership will revive the struggling institution and bring about reform they feel is long overdue. [Russian Academy of Sciences, Russia] Press Release

Cell Therapy Catapult to Work with GlaxoSmithKline on Cell Therapies
The Cell Therapy Catapult will be working with GlaxoSmithKline plc to explore potential collaborations in a range of areas relevant to the development of cell therapies, from research projects to technical and regulatory strategy. [Cell Therapy Catapult] Press Release

Icahn School of Medicine at Mount Sinai Grants Exclusive License to Cellular Dynamics International for Development of a Cellular Therapy for Cardiac Muscles
The Icahn School of Medicine at Mount Sinai has granted Cellular Dynamics International exclusive license rights to commercially develop cardiomyocyte progenitors for in vivo cell therapy and regenerative medicine applications. These cells are capable of further differentiation into the multiple cell types of the heart, including cardiomyocytes, endothelial cells, and vascular smooth muscle cells, and thus could be used as a potential therapeutic for damaged heart tissue. [Icahn School of Medicine at Mount Sinai] Press Release

Stem Cell Agency Awards More than $42 Million in New Research and Leadership Funding
California’s position as a global leader in stem cell research has been strengthened by the awarding of $36 million in funds to attract six world-class scientists to the state, and more than $6 million to create a partnership with Sangamo BioSciences to develop a therapy for beta-thalassemia. [California Institute for Regenerative Medicine] Press Release

Maryland Stem Cell Research Commission Funds 31 New Research Proposals in FY 2013
The Maryland Stem Cell Research Commission has completed its review of the 171 applications received in response to its FY 2013 Requests for Applications. The board of directors of the Maryland Technology Development Corporation approved the Commission’s recommendation to fund 31 new proposals with the Maryland Stem Cell Research Fund’s $10.4 million FY2013 budget. [Maryland Stem Cell Research Fund]
Press Release

Cell Therapy to Fight Skin Cancer
Dr Graham Leggatt of The University of Queensland Diamantina Institute, based at Translational Research Institute, is investigating anti-cancer immune cells as an alternative therapeutic option for non-melanoma skin cancer. His work is being supported by a $100,000 Cancer Council Queensland research grant. [The University of Queensland] Press Release

uniQure and Consortium to Receive EUR 2.5 Million Eurostars Grant to Develop RNAi Gene Therapy for Huntington’s Disease
uniQure B.V. announced that with its consortium partners it is to receive a EUR 2.5 million Eurostars grant to develop an RNA interference (RNAi) gene therapy for Huntington’s disease. The consortium is a pan-European collaboration consisting of uniQure as the coordinator, Lausanne University Hospital, Switzerland, University Medical Center Göttingen, Germany, and Maria Curie-Sklodowska University, Poland. [uniQure B.V.]
Press Release

Pain, Pain, Go Away Gene Therapy at Center of UTMB Effort to Eliminate Neuropathic Pain
University of Texas Medical Branch at Galveston researchers have been awarded a five-year, $1.8 million grant by the National Institute of Neurological Disorders and Stroke to apply the techniques of gene therapy to the problem of neuropathic pain – that is, pain that arises from a malfunction in the nervous system. [University of Texas Medical Branch at Galveston] Press Release

ACT Confirms Clinical Trial Participant Showed Improvement in Vision from 20/400 to 20/40 following Treatment
Advanced Cell Technology, Inc. (ACT) confirmed that the vision of a patient enrolled in a clinical investigation of the company’s retinal pigment epithelial cells derived from human embryonic stem cells has improved from 20/400 to 20/40 following treatment. [Advanced Cell Technology, Inc.] Press Release

NW Bio Initiates Phase III DCVax^®-L Brain Cancer Trial in Europe: King’s College Hospital in the UK Is First Site to Open
Northwest Biotherapeutics announced that its Phase III clinical trial with DCVax^®-L for brain cancer has been initiated at King’s College Hospital in the UK. [Northwest Biotherapeutics, Inc.] Press Release

Cellular Biomedicine Group Announces Enrollment Milestone for Phase I Clinical Trial for Liver Cancer
Cellular Biomedicine Group announced that it has achieved half of the enrollment of the total projected enrollment required for its Phase I trial to evaluate the safety and preliminary efficacy of tumor stem cell specific dendritic cell therapy for hepatocellular carcinoma, the most common type of liver cancer. [Thomson Reuters] Press Release

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Sequester’s 5% Cut Rolls Through Biomedical Labs
National Institutes of Health (NIH) is losing $1.7 billion this year from sequestration and other cuts, lowering its budget to $29.15 billion. New and competing grants are going down by 703, from 8986. As a result, the NIH grant success rate may drop from an already record-low 18% in 2012 to 16%, according to Senator Tom Harkin (D-IA), chair of the Senate spending subcommittee that discussed NIH’s 2014 budget request. Press Release

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NEW CIRM/ARM: Reimbursement Strategies for Stem Cell and Regenerative Medicine
June 20, 10:00AM (PT in US)
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NEW Frontiers in Stem Cells & Regeneration
September 29-October 6, 2013
Woods Hole, United States

NEW ESH/Eurocord-Ed/Eurocord World Cord Blood Congress IV and Innovative Therapies for Sickle Cell Disease
October 24-27, 2013
Monaco, Monaco

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