Cell Therapy News Volume 18.33 | Oct 2 2017

TOP STORY

Cellular Immunotherapy for Septic Shock (CISS): A Phase I Clinical Trial

Scientists conducted a Phase I dose escalation trial of mesenchymal stem (stromal) cells (MSCs) in septic shock with the primary objective to examine the safety and tolerability of MSCs. The infusion of freshly cultured allogenic bone marrow derived MSCs into participants with septic shock up to a dose of three million cells per kg appeared safe. [Am J Respir Crit Care Med] Abstract

(Ranked by impact factor of the journal)

Clinical Responses to Adoptive T-Cell Transfer Can Be Modeled in an Autologous Immune-Humanized Mouse Model

To study adoptive cell transfer (ACT) and immunotherapies in a humanized model, researchers developed PDXv2.0 — a melanoma patient-derived xenograft (PDX) model where tumor cells and tumor-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain knockout mouse. [Nat Commun] Full Article

A Compound Chimeric Antigen Receptor Strategy for Targeting Multiple Myeloma

Investigators report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens, BCMA and CS1. They determined that the resulting compound CAR T-cell possesses consistent, potent, and directed cytotoxicity against each target antigen population. [Leukemia] Abstract | Full Article

Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18

The effects of transgenically encoded human and mouse interkeulin (IL)-18 on T cell proliferation and its application in boosting CAR T cells are presented. Robust enhancement of proliferation of IL-18-secreting human T cells occurred in a xenograft model, and this was dependent on T cell receptor and IL-18R signaling. [Cell Rep] Full Article | Graphical Abstract

Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson’s Disease

Researchers showed that treatment of vitamin C (VC) enhances generation of authentic midbrain-type dopamine (DA) neurons with improved survival and functions from ventral midbrain-derived neural stem/precursor cells (NSCs). Transplantation of VC-treated NSCs resulted in improved behavioral restoration, along with enriched DA neuron engraftment, which faithfully expressed midbrain-specific markers in Parkinson’s disease model rats. [Stem Cell Reports] Full Article | Graphical Abstract

An RNAi Screen Reveals an Essential Role for HIPK4 in Human Skin Epithelial Differentiation from iPSCs

Using an approach including RNAi and high-throughput imaging of early epithelial cells, investigators identified candidate kinases involved in their differentiation from human induced pluripotent stem cells (iPSCs). Among these, they found HIPK4 to be an important inhibitor of this process. [Stem Cell Reports] Full Article

Control of HIV Infection In Vivo Using Gene Therapy with a Secreted Entry Inhibitor

Scientists have shown that soluble CD4 was secreted from gene-modified CD4⁺ T cells, as well as from human umbilical cord blood-derived CD34⁺ hematopoietic stem/progenitor cells (HSPCs), and protected unmodified HIV target cells from infection in vitro. To investigate the in vivo application of this approach, they injected gene-modified HSPCs into NOD/SCID/γc^null mice. [Mol Ther Nucleic Acids] Full Article

Correction of β-Thalassemia Mutant by Base Editor in Human Embryos

Researchers report the first study using base editor system to correct disease mutant in human embryos. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, they found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB −28 site precisely in human embryos. [Protein Cell] Full Article | Editorial

Nanoparticle Delivery of Cas9 Ribonucleoprotein and Donor DNA In Vivo Induces Homology-Directed DNA Repair

The authors demonstrated that a delivery vehicle composed of gold nanoparticles conjugated to DNA and complexed with cationic endosomal disruptive polymers can deliver Cas9 ribonucleoprotein and donor DNA into a wide variety of cell types and efficiently correct the DNA mutation that causes Duchenne muscular dystrophy in mice via local injection, with minimal off-target DNA damage. [Nat Biomed Eng] Abstract | Press Release

Clodronate Improves Survival of Transplanted Hoxb8 Myeloid Progenitors with Constitutively Active GMCSFR in Immunocompetent Mice

Researchers generated Hoxb8-dependent myeloid progenitors (HDPs) by transducing lineage-negative bone marrow cells with a constitutively expressed Hoxb8 flanked by loxP. HDPs proliferated indefinitely and differentiated into macrophages when Hoxb8 was removed by a tamoxifen-inducible Cre. [Mol Ther Methods Clin Dev] Full Article

Chimeric Antigen Receptor T-Cell Therapies for Multiple Myeloma

Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. [Blood] Abstract

Genome Engineering: A New Approach to Gene Therapy for Neuromuscular Disorders

Scientists summarize the genome engineering strategies that are currently under preclinical evaluation for the treatment of degenerative neuromuscular disorders, with a focus on the molecular tools that show the greatest potential for clinical translation of these therapies. [Nat Rev Neurol] Abstract

Gene Therapy with the Sleeping Beauty Transposon System

The authors review the most important aspects of using Sleeping Beauty for gene therapy, including vectorization as well as genomic integration features. They also illustrate the path to successful clinical implementation by highlighting the application of CAR-modified T cells in cancer immunotherapy. [Trends Genet] Abstract

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

TxCell Collaboration Presents New Proof-of-Concept Transplantation Results with Proprietary Second-Generation CAR-Tregs

TxCell SA announced details on the new proof-of-concept preclinical data presented. The oral presentation made by Prof. Megan Levings describes positive data obtained with proprietary second-generation CAR-regulatory T cells (Tregs) in a graft-versus-host disease preclinical model. [Press release from TxCell SA discussing research presented at the 18^th Congress of the European Society for Organ Transplantation (ESOT), Barcelona] Press Release

TxCell to Present Two Posters

TxCell SA announced it will present two posters with new CAR-regulatory T cell related data. [Press release from TxCell SA discussing research to be presented at the 25^th Anniversary Congress of the European Society of Gene & Cell Therapy (ESGCT), Berlin] Press Release

MD Anderson Cancer Center and Pfizer Oncology Announce Clinical Collaboration to Evaluate Immuno-Oncology Combinations in Blood Cancers and Solid Tumors

The University of Texas MD Anderson Cancer Center and Pfizer Inc. announced that they have entered into a clinical collaboration to study novel combinations of three Pfizer investigational immuno-oncology therapies and other Pfizer agents in the treatment of various solid tumors and hematologic malignancies. [The University of Texas MD Anderson Cancer Center] Press Release

Casebia Therapeutics Announces License and Collaboration Agreements with Seattle Children’s Research Institute

Casebia Therapeutics and Seattle Children’s Research Institute announced an exclusive license agreement and research collaboration to explore new methods to treat and prevent autoimmune disease using CRISPR/Cas9 gene-edited regulatory T cells—a type of white blood cell that controls and modulates the body’s immune response. [Casebia Therapeutics] Press Release

BioLineRx Announces Initiation of Phase Ib/II Trial for BL-8040 in AML under Immunotherapy Collaboration

BioLineRx Ltd. announced the initiation of a Phase Ib/II trial for BL-8040 in combination with atezolizumab, an anti-PDL1 cancer immunotherapy from Genentech, a member of the Roche Group. The trial, known as the BATTLE study, will focus on the maintenance treatment of patients with intermediate- and high-risk acute myeloid leukemia (AML) who have achieved a complete response following induction and consolidation therapy. [BioLineRx Ltd.] Press Release

Asterias Announces Two Significant Developments for Spinal Cord Injury Program

Asterias Biotherapeutics, Inc. announced new 12-month data from the first efficacy cohort in the company’s ongoing Phase I/IIa SCiStar study designated to evaluate safety and efficacy of AST-OPC1. The 12-month data showed 67% of Cohort 2 subjects have recovered two or more motor levels on at least one side through 12 months, which is more than double the rates of recovery seen in both matched historical controls and published data in a similar population. [sterias Biotherapeutics, Inc.] Press Release

bluebird bio Announces First Patient Treated with Second Anti-BCMA CAR T bb21217 in CRB-402 Phase I Study in Patients with Relapsed/Refractory Multiple Myeloma

bluebird bio, Inc. announced the treatment of the first patient with relapsed/refractory multiple myeloma in a Phase I study of bb21217. bb21217 is an investigational CAR T cell therapy targeting B cell maturation antigen (BCMA). bluebird bio is developing bb21217 in collaboration with Celgene Corporation. [bluebird bio, Inc.] Press Release

NantKwest Announces Successful First in Human Administration of CD16 High Affinity Natural Killer (haNK) Cells

NantKwest Inc. announced the clinical implementation of the company’s haNK cell therapy program to human clinical trials with the first participants treated in the first-in-human, Phase I haNK cell therapy clinical trial targeting a wide range of cancer types. [NantKwest Inc.] Press Release

Audentes Therapeutics Announces Rare Pediatric Disease and Fast Track Designations for AT132 for the Treatment of X-Linked Myotubular Myopathy

Audentes Therapeutics, Inc. announced that the FDA has granted Rare Pediatric Disease and Fast Track designations for AT132, the company’s gene therapy product candidate being developed to treat X-linked myotubular myopathy. In addition to these two new designations, AT132 has also received Orphan Drug designation from both the FDA and European Medicines Agency. [Audentes Therapeutics, Inc.] Press Release

Sangamo and Bioverativ Announce FDA Acceptance of IND Application for ST-400 — a Gene-Edited Cell Therapy Candidate — to Treat Beta-Thalassemia

Sangamo Therapeutics, Inc. and Bioverativ Inc. announced that the FDA has accepted the Investigational New Drug (IND) application for ST-400, a gene-edited cell therapy candidate for people with transfusion-dependent beta-thalassemia. [Sangamo Therapeutics, Inc.] Press Release

Bone Therapeutics and Asahi Kasei Sign Exclusive License Agreement for PREOB^® in Japan

Bone Therapeutics announced it has signed an exclusive, royalty-bearing license agreement with one of Japan’s leading industrial companies, Asahi Kasei Corporation. The license agreement covers the development and commercialization of Bone Therapeutics’ autologous bone cell therapy product, PREOB^®, in Japan. [Bone Therapeutics S.A.] Press Release

Inga Hofmann Named Medical Director of Program for Advanced Cell Therapy

The Program for Advanced Cell Therapy, a collaboration of the University of Wisconsin School of Medicine and Public Health and University of Wisconsin (UW) Carbone Cancer Center, has chosen its first medical director. Dr. Inga Hofmann, assistant professor of pediatric hematology, oncology and bone marrow transplant at the UW School of Medicine and Public Health, will assume the medical director role at the recently completed $1 million addition to the Clinical Hematopoietic Cell Processing Laboratory at University Hospital. [University of Wisconsin School of Medicine and Public Health] Press Release

After Upheaval, Russian Academy of Sciences Gets New Leader

After months of uncertainty, the Russian Academy of Sciences finally has a new leader. Russian President Vladimir Putin approved physicist Alexander Sergeyev as the academy’s president for the next five years. Sergeyev has vowed to secure more money for Russian science and create a fund, through a new tax on fossil fuel company profits, for upgrading the country’s antiquated research infrastructure. [ScienceInsider] Editorial

Researchers Caught in Growing Rift over Catalan Independence

Scientists in Catalonia are feeling the ripples of a severe crisis as the region’s bid for independence from Spain comes to a head. [ScienceInsider] Editorial

French Government Proposes Big Science-Spending Boost

French research funding is set for a heartening increase in the country’s first budget under President Emmanuel Macron, if draft 2018 plans are voted into law. [Nature News] Editorial

How the Latest US Travel Ban Could Affect Science

The latest version of US President Donald Trump’s travel ban could make it harder for researchers from several countries to enter the United States to attend scientific meetings, perform research or visit relatives. [Nature News] Editorial

Canada Names New Chief Science Adviser

Mona Nemer, a cardiology researcher and vice-president of research at the University of Ottawa, has been named Canada’s new Chief Science Adviser by Prime Minister Justin Trudeau. [ScienceInsider] Editorial

FDA

Classification of Products as Drugs and Devices and Additional Product Classification Issues; Guidance for Industry and Food and Drug Administration Staff; Availability (FR Doc. No:2017-20522) Notice

NEW The 2018 World Stem Cell Summit (WSCS)
January 22-26, 2018
Miami, Florida, United States

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NEW Postdoctoral Position – Development of Gene Therapy (Vitalité Health Network, Université de Moncton)

NEW Non-Clinical Lecturer – Respiratory Gene Therapy (Imperial College London)

Research Technologist – Immunotherapy (STEMCELL Technologies Inc.)

Research Associate – Infection and Immunity (University College London)

Research Scientist – Immuno-Oncology (Kymab Ltd)

Technologist – Cell Therapy (Yale New Haven Health)

Researcher – Skeletal Tissue Engineering (KU Leuven)

Postdoctoral Fellow – Cell Biology, Tumor Immunology and Targeted Therapy (University of Minnesota)

Postdoctoral Associate – Enhancer RNA Therapy (Sylvester Comprehensive Cancer Center)

Research Fellow – Functional Roles of Stem Cell Derived Extracellular Vesicles (Mayo Clinic)

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

Postdoctoral Fellow – Various Projects (University of Oklahoma)

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