Cell Therapy News Volume 20.42 | Dec 16 2019

TOP STORY

Targeting REGNASE-1 Programs Long-Lived Effector T Cells for Cancer Therapy

The authors used an in vivo pooled CRISPR-Cas9 mutagenesis screening approach to demonstrate that, by targeting REGNASE-1, CD8⁺ T cells were reprogrammed to long-lived effector cells with extensive accumulation, better persistence and robust effector function in tumors. REGNASE-1-deficient CD8⁺ T cells showed markedly improved therapeutic efficacy against mouse models of melanoma and leukemia. [Nature] Abstract

(Ranked by impact factor of the journal)

Gene Therapy for Progressive Familial Intrahepatic Cholestasis Type 3 in a Clinically Relevant Mouse Model

Researchers report results from treating two- or five-week-old Abcb4^-/- mice with an AAV vector expressing human ABCB4, resulting in significant decreases of PFIC3 disease biomarkers. All male mice achieved a sustained therapeutic effect up through 12 weeks, but the effect was achieved in only 50% of females. [Nat Commun] Full Article

Transplantation of Mesenchymal Stem Cells Causes Long-Term Alleviation of Schizophrenia-Like Behavior Coupled with Increased Neurogenesis

Investigators utilized intracerebroventricular transplantation of bone marrow-derived mesenchymal stem cells (MSCs) as a means to enhance hippocampal neurogenesis in the ketamine-induced neurodevelopmental murine model for schizophrenia. Syngeneic MSCs successfully engrafted and survived for up to three months following transplantation. [Mol Psychiatry] Abstract

A Systematic Capsid Evolution Approach Performed In Vivo for the Design of AAV Vectors with Tailored Properties and Tropism

With the BRAVE approach, virus particle displayed a peptide, derived from a protein, of known function on the AAV capsid surface, and a unique molecular barcode in the packaged genome. The sequencing of RNA-expressed barcodes from a single-generation in vivo screen allows the mapping of putative binding sequences from hundreds of proteins simultaneously. [Proc Natl Acad Sci USA] Abstract | Press Release

Novel Cell-Permeable p38-MAPK Inhibitor Efficiently Prevents Porcine Islet Apoptosis and Improves Islet Graft Function

To evaluate the effects of 11R‐p38I110, porcine islets were incubated with 10 µM 11R-p38I₁₁₀ or a mutant form designated 11R-mp38I₁₁₀. After islet transplantation, blood glucose levels reached the normoglycemic range in 58.3% and 0% of diabetic mice treated with 11R-p38I₁₁₀ or 11R-mp38I₁₁₀, respectively. [Am J Transplant] Abstract

Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

Scientists showed that conformally coated stem-cell (SC) islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC derived islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. [Stem Cell Reports] Full Article

Enteric Neuronal Cell Therapy Reverses Architectural Changes in a Novel Diphtheria Toxin-Mediated Model of Colonic Aganglionosis

Researchers developed a novel model of aganglionosis in which enteric neural crest-derived cells express diphtheria toxin (DT) receptor. Local DT injection into the colon wall resulted in focal, specific, and sustained enteric nervous system ablation without altering gastrointestinal transit or colonic contractility, allowing improved survival over other aganglionosis models. [Sci Rep] Full Article

Cell-Based Interferon Gene Therapy Using Proliferation-Controllable, Interferon-Releasing Mesenchymal Stem Cells

Investigators tried to control the amount of murine interferon-γ (IFN-γ) secreted from transplanted murine mesenchymal stem cell line C3H10T1/2 cells to achieve safe cell-based IFN-γ gene therapy for cancer. C3H10T1/2 cells were transfected with HSVtk- and murine IFN-γ-expressing plasmid vectors to obtain C3H10T1/2/HSVtk/IFN-γ cells. C3H10T1/2/HSVtk/IFN-γ cells released IFN-γ and were sensitive to ganciclovir. [Sci Rep] Full Article

Ex/In Vivo Gene Editing in Hepatocytes Using “All-in-One” CRISPR-AAV Vectors with a Self-Linearizing Repair Template

The vector genome of 5.73 kb was packaged into VP2-depleted adeno-associated virus (AAV) particles, which did not improve cargo capacity. Reprogrammed hepatocytes were treated with AI-SL.AAV2^ΔVP2 and subsequently transplanted, resulting large clusters of FAH-positive hepatocytes. [iScience] Abstract | Graphical Abstract

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The Influence of Environment and Origin on Brain Resident Macrophages and Implications for Therapy

The authors review the emerging literature and discuss the potential implications of origin on microglial function, with particular focus on existing and future therapies using bone-marrow- or stem-cell-derived cells for the treatment of neurological diseases. [Nat Neurosci] Abstract

Chimeric Antigen Receptor T-Cell Therapy for Multiple Myeloma: A Consensus Statement from the European Myeloma Network

The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent Phase I/II trials show promising preliminary results in patients with multiple myeloma progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. [Haematologica] Abstract

Targeting Innate Sensing in the Tumor Microenvironment to Improve Immunotherapy

Investigators review the innate sensing pathways related to cancer initiation/progression and therapies, summarize the recent key findings in innate immune sensing related to conventional therapies, evaluate current combination strategies, and highlight the potential issues of combinational therapies in terms of antitumor efficacy and toxicities. [Cell Mol Immunol] Abstract

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GenEdit and Editas Medicine Enter into Exclusive License and Collaboration Agreement for Nanoparticle Gene Therapy Delivery

GenEdit, Inc. announced that it has entered into a worldwide, exclusive license and collaboration agreement with Editas Medicine, Inc., a genome editing company. [GenEdit, Inc. (Business Wire, Inc.)] Press Release

Anixa Biosciences Provides Update on CAR-T Program

Anixa Biosciences, Inc. announced an update regarding the CAR-T technology it is developing with its partner, Moffitt Cancer Center. Experimental results reported from the laboratory of Dr. Jose Conejo-Garcia, the inventor of Anixa’s CAR-T technology and the Chair of the Department of Immunology at Moffitt, indicate that the potential efficacy of this technology as a treatment for ovarian cancer could be greatly improved through additional genetic engineering. [Anixa Biosciences, Inc.] Press Release

WindMIL Therapeutics Announces Dosing of First Patient in a Phase IIa Clinical Trial of Marrow-Infiltrating Lymphocytes (MILs™) for Treatment of Patients with Non-Small Cell Lung Cancer

WindMIL Therapeutics announced that the first patient has been dosed in a Phase IIa clinical trial to determine the safety and efficacy of MILs alone and in combination with an anti-PD-1 in patients with locally advanced unresectable or metastatic non-small cell lung cancer who are refractory to or have relapsed on an anti-PD-1-containing regimen. [WindMIL Therapeutics] Press Release

Gritstone Oncology Reports Promising Early Immunogenicity Activity and Safety Data from Its Phase I Studies Evaluating Its Neoantigen-Based Immunotherapies, GRANITE and SLATE

Gritstone Oncology, Inc. announced that the company has presented preliminary Phase I GRANITE immunogenicity data demonstrating the rapid, robust and consistent induction of large numbers of CD8⁺ T cells against multiple neoantigens in four solid tumor patients with available IFN-g ELISpot data within the first two dosing cohorts. [Gritstone Oncology, Inc.] Press Release

UK Election Dashes Scientists’ Hopes of Staying in the EU

The United Kingdom is now firmly on the path towards leaving the European Union, after the Conservative party won a majority of 79 seats in yesterday’s general election – a result that has major implications for science. [Nature News] Editorial

United States Drops Charges against Two More Scientists after Iran Prisoner Swap

US authorities have dropped charges against two researchers accused of attempting to export chemicals to Iran in violation of trade sanctions. The decision follows a prisoner swap in which the United States freed a third researcher who was charged alongside them – and imprisoned. [Nature News] Editorial

FDA

Regulation Requiring an Approved New Drug Application for Drugs Sterilized by Irradiation (FR Doc. No:2019-27046) Notice

MHRA

MHRA Guidance and Publications About a Possible No-Deal Brexit Notice

NEW Tuberculosis: Immunity and Immune Evasion
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