Cell Therapy News Volume 20.40 | Dec 2 2019

TOP STORY

An Acute Immune Response Underlies the Benefit of Cardiac Stem-Cell Therapy

The authors examined the mechanistic basis for cell therapy in mice after ischemia/reperfusion injury, and while heart function was enhanced, it was not associated with new cardiomyocyte production. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2⁺ and CX3CR1⁺ macrophages. [Nature] Abstract | Press Release | Editorial

(Ranked by impact factor of the journal)

CRISPRSwitch Regulates sgRNA Activity by Cre Recombination for Sequential Editing of Two Loci

The authors developed a precisely controlled sgRNA expression cassette that could be combined with widely-used Cre systems, termed SgRNA With Induction/Termination by Cre Homologous recombination (CRISPR-Switch). Switch-ON facilitates controlled, rapid induction of sgRNA activity. In turn, Switch-OFF-mediated termination of editing improves generation of heterozygous genotypes and can limit off-target effects. [Nat Commun] Full Article

Efficacy of Third-Party Chimeric Antigen Receptor Modified Peripheral Blood Natural Killer Cells for Adoptive Cell Therapy of B-Cell Precursor Acute Lymphoblastic Leukemia

Scientists developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. [Leukemia] Abstract

Enterotoxins Can Support CAR T Cells against Solid Tumors

Researchers investigated if inducing an interaction between CAR T cells and antigen-presenting cells (APCs) in lymphoid tissue, away from an immunosuppressive microenvironment, could enhance solid-tumor responses. They combined CAR T cell transfer with the bacterial enterotoxin staphylococcal enterotoxin-B, which naturally linked a proportion of T cell receptor Vβ subtypes to MHC-II, present on APCs. [Proc Natl Acad Sci USA] Abstract

MDM2 Inhibitor APG-115 Synergizes With PD-1 Blockade Through Enhancing Antitumor Immunity in the Tumor Microenvironment

Using APG-115 that is a MDM2 antagonist in clinical development as a pharmacological p53 activator, scientists investigated the role of p53 in immune modulation and combination therapy with PD-1 blockade. [J Immunother Cancer] Full Article

Expanding CAR T Cells in Human Platelet Lysate Renders T Cells With In Vivo Longevity

Second generation chimeric antigen receptor with CD28 and CD3ζ endodomain targeting prostate stem cell antigen or CD19-were constructed and used for this study. After retroviral transduction, CAR T cells were divided into three conditions containing either fetal bovine serum, human AB serum or human platelet lysate and expanded for seven days. [J Immunother Cancer] Full Article

Effective and Accurate Gene Silencing by a Recombinant AAV-Compatible MicroRNA Scaffold

The authors report that embedding the guide strand of a small silencing RNA into an artificial miRNA scaffold derived from mouse miRNA-33 ensured rAAV genomic integrity and reduced off-targeting by ten-fold, while maintaining effective in vivo target gene repression in mice. [Mol Ther] Abstract | Graphical Abstract

Liver-Directed but Not Muscle-Directed AAV-Antibody Gene Transfer Limits Humoral Immune Responses in Rhesus Monkeys

Scientists investigated different AAV vector strategies and delivery schemes to rhesus monkeys using the rhesus monkey mAb 4L6. They compared 4L6 IgG1 delivery using the AAV1 vs. the AAV8 serotype with a CMV promoter and the use of a muscle-specific vs. a liver-specific promoter. Long-term expression levels of 4L6 IgG1 following AAV8-mediated gene transfer were comparable to those following AAV1-mediated gene transfer. [Mol Ther Methods Clin Dev] Abstract | Full Article

Minimally Invasive Delivery of Microbeads with Encapsulated, Viable and Quiescent Neural Stem Cells to the Adult Subventricular Zone

Researchers describe the use of polyethylene glycol microbeads for the coincident delivery of endothelial cells (EC) and neural stem cells (NSC) as a means of enhancing appropriate NSC quiescence and survival during transplantation into the mouse brain. They demonstrated that EC and NSC co-encapsulation maintained NSC quiescence, enhanced NSC viability, and facilitated NSC extravasation in vitro, as compared to NSC encapsulated alone. [Sci Rep] Full Article

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Human Germline Genome Editing

Unresolved questions about pre-implantation human development could be addressed by basic research using CRISPR-Cas9. The authors discuss advances in human genome editing and consider ethical questions and potential clinical implications of this technology. [Nat Cell Biol] Abstract

Editing Cytoprotective Autophagy in Glioma: An Unfulfilled Potential for Therapy

Clinical trials for glioblastoma (GBM) continue to fall short of showing significant survival or clinical benefit, with the complex glioma heterogeneity often being the reason to blame. Scientists propose that a combination therapy of current antiglioma regimens and autophagic mediators or suppressors can allow us to overcome GBM regrowth in the context of tumor heterogeneity. [Trends Mol Med] Abstract

CRISPR Diagnosis and Therapeutics With Single Base Pair Precision

CRISPR has been widely accepted as a versatile genome editing tool with significant potential for medical application. Reliable allele specificity is one of the most critical elements for successful application of this technology to develop high-precision therapeutics and diagnostics. [Trends Mol Med] Abstract

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Cyrus Biotechnology and the Broad Institute of MIT and Harvard Launch Multi-Target Collaboration to Develop Optimized CRISPR Gene Editing Technology

Cyrus Biotechnology, Inc. and the Broad Institute of MIT and Harvard have embarked on a scientific collaboration to optimize CRISPR for use in developing novel human therapeutics. [Cyrus Biotechnology, Inc.] Press Release

First-in-Kind Human 3-Dimensional Models of Parkinson’s Disease and Progressive Multiple Sclerosis Launching to the International Space Station

The National Stem Cell Foundation announced that research teams from Aspen Neuroscience and the New York Stem Cell Foundation Research Institute will send a first-in-kind study of neurodegenerative disease to the International Space Station on the nineteenth SpaceX Commercial Resupply Services mission, scheduled to launch December 4^th from the Kennedy Space Center in Cape Canaveral, Florida. [The National Stem Cell Foundation] Press Release

Elsevier Progresses in Open-Access Deal Making

The scholarly publisher has announced several new licensing agreements in both Europe and the US, but some major academic groups are still without contracts and access to journals. [The Scientist] Editorial

Chinese Ministry Investigates Duplications in Papers by University President

The Chinese education ministry is investigating scientific articles authored by high-profile immunologist and university president Cao Xuetao, following suggestions that dozens of papers contain potentially problematic images. Four journals also say they are examining papers from Cao. [Nature News] Editorial

FDA

Adaptive Designs for Clinical Trials of Drugs and Biologics; Guidance for Industry; Availability (FR Doc. No:2019-25986) Notice

NEW Keystone Symposia: Noncoding RNAs – Mechanism, Function and Therapies
January 12-16, 2020
Whistler, British Columbia, Canada

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NEW Postdoctoral Researcher – (Ciliopathies and Neurogenetics (University of Alberta)

NEW Postdoctoral Researcher – Wnt Signaling (German Cancer Research Center in the Helmholtz Association)

NEW Technical Officer – Micro-Injectionist (European Molecular Biology Laboratory)

Junior Research Fellow – Synthetic Biology (Dresden University of Technology)

Post-doctoral fellow – Cancer Immunology/Bioengineering (West Virginia University)

Postdoctoral Fellow – Cancer Research (BC Cancer)

Research Assistant – Cancer Research (BC Cancer)

Postdoctoral Fellow – Cancer Therapy (Purdue University)

Postdoctoral Fellow – Single Cell Genomics (BC Cancer)

Tenure Track Faculty Position – Cancer Biology & Therapeutics (Geisel School of Medicine at Dartmouth)

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