Cell Therapy News Volume 20.35 | Oct 21 2019

TOP STORY

Multiplexed Activation of Endogenous Genes by CRISPRa Elicits Potent Antitumor Immunity

Investigators leveraged CRISPR activation (CRISPRa) to directly augment the in situ expression of endogenous genes, and thereby the presentation of tumor antigens, leading to dramatic antitumor immune responses. [Nat Immunol] Abstract

(Ranked by impact factor of the journal)

T Cells Redirected against IGβ for the Immunotherapy of B Cell Lymphoma

The authors engineered T cells to express anti-Igβ CAR with CD28 costimulatory signaling moiety, and observed that Igβ-CAR T cells could efficiently recognize and eliminate Igβ⁺ lymphoma cells both in vitro and in two different lymphoma xenograft models. [Leukemia] Abstract

Imaging CAR T Cell Trafficking with eDFHR as a PET Reporter Gene

Engineered T cells showed approximately a 50-fold increased bioluminescent imaging signal, and a 10-fold increased [¹⁸F]-trimethoprim uptake compared to controls in vitro. E. coli dihydrofolate reductase enzyme (eDFHR)-expressing anti-GD2 CAR T cells were injected into mice bearing control GD2^– and GD2⁺ tumors. [Mol Ther] Abstract | Graphical Abstract

Plasmid-Mediated Gene Therapy in Mouse Models of Limb Girdle Muscular Dystrophy

Researchers delivered plasmid DNA encoding therapeutic genes to the muscles of mouse models of limb girdle muscular dystrophy 2A, 2B, and 2D, deficient in calpain3, dysferlin, and alpha-sarcoglycan, respectively. They also delivered the human follistatin gene, which has the potential to increase therapeutic benefit. [Mol Ther Methods Clin Dev] Abstract | Full Article

Transplantation of Pegylated Islets Enhances Therapeutic Efficacy in a Diabetic Nonhuman Primate Model

Scientists modified a pancreatic islet surface with long-chain poly(ethylene glycol) (PEG) to mitigate detrimental host-implant interactions. The effect of PEGylation on islet engraftment and long-term survival was examined in a robust nonhuman primate model via three paired transplants of dosages 4,300, 8,300, and 10,000 IEQ/kg. [Am J Transplant] Abstract

Combined NK Cell Therapy and Radiotherapy Exhibit Long-Term Therapeutic and Anti-Metastatic Effects in a Human Triple Negative Breast Cancer Model

Reduction in tumor burden by combining radiotherapy and systemic natural killer (NK) cell therapy improved the suppression of primary tumor growth, with efficient NK cell migration and penetration into the primary tumor site. [Int J Radiat Oncol Biol Phys] Abstract

Anti-Inflammatory and Vasculogenic Conditioning of Peripheral Blood Mononuclear Cells Reinforces Their Therapeutic Potential for Radiation-Injured Salivary Glands

The authors developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs) and investigated whether such effectively conditioned PBMNCs could regenerate radiation-injured salivary glands and ameliorate salivary secretory function in mice. [Stem Cell Res Ther] Full Article

First-in-Human High-Cumulative-Dose Stem Cell Therapy in Idiopathic Pulmonary Fibrosis with Rapid Lung Function Decline

Scientists evaluated the safety, tolerability, and efficacy a of high cumulative dose of bone marrow mesenchymal stem cells in patients with a rapid progressive course of severe to moderate idiopathic pulmonary fibrosis. [Stem Cells Transl Med] Full Article

Molecular Engineering of Adeno-Associated Virus Capsid Improves Its Therapeutic Gene Transfer in Murine Models of Hemophilia and Retinal Degeneration

Intravitreal gene transfer of glycosylation site modified vectors in C57BL6/J mice demonstrated an enhanced EGFP expression (~2 to 4-fold) and enhanced permeation across retina. [Mol Pharm] Abstract

Survival of Aging CD264⁺ and CD264^– Populations of Human Bone Marrow Mesenchymal Stem Cells Is Independent of Colony-Forming Efficiency

Counterintuitive to their aging phenotype, CD264⁺ human bone marrow mesenchymal stem cells (hBM-MSCs) exhibited comparable survival to matched CD264^– hBM-MSCs from the same culture during in vitro colony formation and in vivo when implanted ectopically in immunodeficient NIH III mice. [Biotechnol Bioeng] Abstract

Human Adipose-Derived Pericytes Display Steroidogenic Lineage Potential In Vitro and Influence Leydig Cell Regeneration In Vivo in Rats

In vivo, no difference in Leydig cell-regeneration was noted between Sham and human adipose-derived perivascular stem cell (hAd-PSC)-transplanted rats. Cyp17a1 expression increased in hAd-PSC-transplanted testes compared to intact vehicle controls and the luteinising hormone/testosterone ratio returned to vehicle control levels which was not the case in EDS⁺ Sham animals. [Sci Rep] Full Article

The Effect of Mesenchymal Stem Cell Sheets on Early Healing of the Achilles Tendon in Rats

Scientists investigated the efficacy of interposed scaffold-free bone marrow derived mesenchymal stem cell (BMSC) sheets on early Achilles tendon healing in rats. BMSCs were isolated from the femora and tibias of male Sprague-Dawley rats aged 8 to 12 weeks and BMSC sheets were produced on temperature-responsive culture dishes. [Tissue Eng Part A] Abstract

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Tolerance Regeneration by T Regulatory Cells in Autologous Haematopoietic Stem Cell Transplantation for Autoimmune Diseases

Scientists review recent research findings on the role of CD4⁺ T regulatory cells in resetting the immune system leading to the eradication of the autoimmune disease after transplantation. [Bone Marrow Transplant] Abstract

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CRISPR Therapeutics and KSQ Therapeutics Announce License Agreement to Advance Companies’ Respective Cell Therapy Programs in Oncology

CRISPR Therapeutics and KSQ Therapeutics announced a license agreement whereby CRISPR Therapeutics will gain access to KSQ intellectual property (IP) for editing certain novel gene targets in its allogeneic oncology cell therapy programs, and KSQ will gain access to CRISPR Therapeutics’ IP for editing novel gene targets identified by KSQ as part of its current and future eTIL^™ cell programs. [CRISPR Therapeutics] Press Release

Mesoblast and Lonza Enter into Agreement for Commercial Manufacture of Mesoblast’s Potential First United States Allogeneic Cell Therapy

Mesoblast and Lonza announced that they have entered into an agreement for the commercial manufacture of Mesoblast’s lead allogeneic cell therapy product candidate, remestemcel-L, for pediatric steroid-refractory acute graft versus host disease. [Mesoblast] Press Release

Editas Medicine and AskBio Enter Strategic Research Collaboration to Explore In Vivo Delivery of Genome Editing Medicines to Treat Neurological Diseases

Editas Medicine, Inc. and Asklepios BioPharmaceutical, Inc. announced the companies have entered a strategic research collaboration to explore in vivo delivery of genome editing medicines to treat neurological diseases. [Editas Medicine, Inc.] Press Release

Adaptate Biotherapeutics Formed to Develop Antibody-Based Therapies that Modulate Gamma Delta T-Cells

GammaDelta Therapeutics announced the formation of a spin-out company: Adaptate Biotherapeutics. While GammaDelta Therapeutics’ primary goal is to develop γδ T-cell based cell therapy products, the new spin-out will build on GammaDelta’s knowledge to modulate γδ T-cell activity using therapeutic antibodies, with the potential to trigger an immune response against cancer. [GammaDelta Therapeutics] Press Release

Abeona Therapeutics Announces Publication of Positive Long-Term Data from Phase I/IIa Clinical Trial Evaluating EB-101 Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

Abeona Therapeutics Inc. announced positive long term efficacy and safety results from its Phase I/IIa clinical trial evaluating EB-101, a gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa. [Abeona Therapeutics Inc.] Press Release

Jazz Pharmaceuticals Announces First Patient Enrolled in Phase II Clinical Trial Evaluating Defibrotide for the Prevention of CAR-T Associated Neurotoxicity

Jazz Pharmaceuticals plc announced that the first patient has been enrolled in an exploratory Phase II clinical trial evaluating the ability of defibrotide to prevent neurotoxicity in patients with relapsed or refractory diffuse large B-cell lymphoma receiving CAR T-cell therapy. [Jazz Pharmaceuticals plc] Press Release

Hope Biosciences Opens First Phase I/II Stem Cell Trial for Brain Injury Treatment

Hope Biosciences announced that enrollment is now open for a Phase I/II trial evaluating safety and efficacy of Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells for traumatic brain injury and hypoxic-ischemic encephalopathy, in partnership with the University of Texas Health Science Center at Houston. [Hope Biosciences] Press Release

UCLA Opens Pioneering CAR T Clinical Trial Aimed at Extending the Lives of People Diagnosed with the Most Common Types of Lymphoma and Leukemia

The UCLA Jonsson Cancer Center has launched a pioneering CAR T cell immunotherapy trial that will attack cancer cells by simultaneously recognizing two targets – CD19 and CD20 – that are expressed on B-cell lymphoma and leukemia. [UCLA Jonsson Comprehensive Cancer Center] Press Release

PharmaCyte Biotech Successfully Completes Manufacturing of Clinical Trial Product

PharmaCyte Biotech, Inc. announced that its partner, Austrianova Singapore, has completed the first of two staggered and back to back manufacturing runs for the production of PharmaCyte’s clinical trial product. [PharmaCyte Biotech, Inc.] Press Release

Russian ‘CRISPR-Baby’ Scientist Has Started Editing Genes in Human Eggs with Goal of Altering Deaf Gene

Russian biologist Denis Rebrikov has started gene editing in eggs donated by women who can hear to learn how to allow some deaf couples to give birth to children without a genetic mutation that impairs hearing. [Nature News] Editorial

$3 Billion Ballot Proposition Will Decide Fate of Texas Cancer Research Funding Agency

On November 5, Texas residents will decide whether to sustain CPRIT, the second largest public source of cancer funding in the United States after the federal government. At stake is its generous support for 123 tenure-track faculty. [ScienceInsider] Editorial

Indian Government Tightens Rules on Academic Collaboration with China

India is tightening the rules for academic collaborations with its neighbor and main rival, China. Under a new policy, universities and research institutes must seek permission from the ministries of Home Affairs and External Affairs before signing a collaboration agreement or memorandum of understanding with a Chinese institution. [ScienceInsider] Editorial

Brexit Hits UK Science Funding and Workforce

The first figures have emerged demonstrating that Brexit uncertainty has adversely affected UK research. They show Britain’s annual share of EU research funding has fallen by nearly a third since 2015. [The BBC] Editorial

FDA

Investigational In Vitro Diagnostics in Oncology Trials: Streamlined Submission Process for Study Risk Determination; Guidance for Industry; Availability (FR Doc. No:2019-22117) Notice

NEW Precision Health: Molecular Basis, Technology and Digital Health
November 13-16, 2019
Heidelberg, Germany

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NEW Postdoctoral Researchers – Cancer Research (German Research Center)

Tenure-Track Faculty Position – Cancer Biology and Therapeutics (Geisel School of Medicine)

Postdoctoral Fellow – Cancer Research (BC Cancer)

Research Assistant – Cancer Research (BC Cancer)

Postdoctoral Fellow – Cancer Research (Baylor College of Medicine)

Postdoctoral Fellow – Molecular Genetic Basis of Behavioral Variation (University of California, San Francisco)

Postdoctoral Fellow – Cancer Therapy (Purdue University)

Research Scientist – Cellular Electrophysiology (Duke 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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