Cell Therapy News Volume 20.23 | Jul 8 2019

TOP STORY

A Fully Human Transgene Switch to Regulate Therapeutic Protein Production by Cooling Sensation

By functionally linking human transient receptor potential melastatin 8 (hTRPM8)-induced signaling to a synthetic promoter containing elements that bind nuclear factor of activated T cells, a synthetic gene circuit was designed that could be adjusted by exposure to either a cool environment or menthol. It was shown that this gene switch was functional in various cell types and human primary cells, as well as in mice implanted with engineered cells. [Nat Med] Abstract | Editorial

(Ranked by impact factor of the journal)

Allele-Specific Gene Editing Prevents Deafness in a Model of Dominant Progressive Hearing Loss

The authors identified a protospacer-adjacent motif variant of Staphylococcus aureus Cas9 (SaCas9-KKH) that selectively and efficiently disrupted the mutant allele, but not the wild-type Tmc1/TMC1 allele, in Beethoven mice and in a DFNA36 human cell line. Adeno-associated virus-mediated SaCas9-KKH delivery prevented deafness in Beethoven mice up to one year post injection. [Nat Med] Abstract | Press Release

In Situ Manipulation of Dendritic Cells by an Autophagy-Regulative Nanoactivator Enables Effective Cancer Immunotherapy

Investigators designed a nanoactivator that manufactured dendritic cells (DCs) through autophagy upregulating in vivo directly, which led to high-efficiency antigen presention of DCs and antigen-specific T cell generation. The nanoactivator significantly enhanced tumor antigen cross-presentation and subsequent T cell priming. [ACS Nano] Abstract | Graphical Abstract

Bone-Targeting AAV-Mediated Silencing of Schnurri-3 Prevents Bone Loss in Osteoporosis

Scientists demonstrated that a recombinant adeno-associated virus (AAV) 9 was highly effective for transducing osteoblast lineage cells in the bone. The adaptor protein schnurri-3 (SHN3) is a promising therapeutic target for osteoporosis, as deletion of shn3 prevented bone loss in osteoporotic mice and short-term inhibition of shn3 in adult mice increased bone mass. [Nat Commun] Full Article

Relaxin Gene Delivery Mitigates Liver Metastasis and Synergizes with Check Point Therapy

In colorectal, pancreatic, and breast cancer liver metastasis models, investigators confirmed that relaxin gene therapy resulted in significant inhibition of metastatic progression and prolonged survival. [Nat Commun] Full Article

Targeting Hypoxia Downstream Signaling Protein, CAIX, for CAR-T Cell Therapy against Glioblastoma

The authors demonstrated that carbonic anhydrase IX (CAIX) was a suitable target for CAR-T therapy using anti-CAIX CAR-T cells against glioblastoma in vitro and in vivo. In their mouse model, a 20% cure rate was observed without detectable systemic effects. [Neuro Oncol] Full Article

Long-Term Safety and Efficacy of Gene/Pulmonary Macrophage Transplantation Therapy of Pulmonary Alveolar Proteinosis in Csf2ra^−/− Mice

Scientists report on the preclinical safety, tolerability and efficacy of lentiviral vector-mediated Csf2ra expression in macrophages and pulmonary macrophage transplantation of gene-corrected macrophages in Csf2ra gene-ablated mice. [Mol Ther] Abstract

AAV9 Edits Muscle Stem Cells in Normal and Dystrophic Adult Mice

CRISPR-treated and untreated muscles were grafted to immune-deficient, dystrophin-null NSG.mdx4cv mice. Grafts regenerated from CRISPR treated muscle contained the edited genome and yielded 2.7-fold more dystrophin⁺ cells. [Mol Ther] Abstract

Translational Assessment of a Genetic Engineering Methodology to Improve Islet Function for Transplantation

Pseudoislets produced from mouse dissociated islet cells displayed basic functions similar to intact native islets in terms of glucose induced intracellular signaling and insulin release, and after transplantation were properly vascularized and contributed to blood glucose homeostasis. [EBioMedicine] Full Article

Optochemogenetics Stimulation of Transplanted iPS-NPCs Enhances Neuronal Repair and Functional Recovery after Ischemic Stroke

Investigators tested the hypothesis that selective excitation of transplanted induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) could recapitulate an activity-enriched microenvironment that confers regenerative benefits for the treatment of stroke. [J Neurosci] Abstract

Stable Intracerebral Transplantation of Neural Stem Cells for the Treatment of Paralysis Due to Ischemic Stroke

In a single‐site, Phase I study, researchers evaluated the feasibility and safety of NSI-566 transplantation for the treatment of hemiparesis due to chronic motor stroke and determined the maximum tolerated dose for future trials. [Stem Cells Transl Med] Full Article

First-in-Human Trial of rhIL-15 and Haploidentical Natural Killer Cell Therapy for Advanced Acute Myeloid Leukemia

Forty-two patients received either intravenous or subcutaneous recombinant human IL-15 (rhIL-15) after lymphodepleting chemotherapy and haploidentical natural killer (NK) cells. Escalating doses of rhIL-15 were given on 12 consecutive days in a Phase I trial. Of 26 patients, 36% had robust in vivo NK-cell expansion at day 14, and 32% achieved complete remission. [Blood Adv] Full Article | Graphical Abstract

Subscribe to one of our other 19 science newsletters such as Mesenchymal Cell News & ESC & iPSC News.

Induced Pluripotent Stem Cell (iPSC)-Derived Lymphocytes for Adoptive Cell Immunotherapy: Recent Advances and Challenges

iPSCs can be a source of broadly applicable cellular immunotherapeutics, which have been manufactured, validated, and banked in advance, and can be applied across HLA barriers. Scientists discuss the recent advances and challenges in the generation of iPSC-derived cellular products for cancer therapy. [Curr Hematol Malig Rep] Full Article

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

Novavax and Catalent Biologics Enter Strategic Partnership: Allowing Catalent Biologics to Expand Gene Therapy Footprint with Acquisition of Novavax’ Manufacturing Assets and Capabilities

Novavax, Inc. and Catalent Biologics’ Paragon Gene Therapy unit announced an arrangement under which Paragon Gene Therapy will assume the leases to two Novavax product development and manufacturing facilities, giving it immediate access to state-of-the-art manufacturing equipment, people and space to accelerate the growth of its gene therapy development and manufacturing business. [Novavax, Inc.] Press Release

ERYTECH Announces Immune Modulation Strategic Collaboration with SQZ Biotechnologies

ERYTECH Pharma announced that it has entered into an agreement with SQZ Biotechnologies to advance novel red blood cell-based therapeutics for immune modulation. [ERYTECH Pharma] Press Release

Amicus Therapeutics and Catalent Biologics Enter Strategic Partnership for Gene Therapy Development and Manufacturing

Amicus Therapeutics, Inc. has entered into a strategic manufacturing agreement with Paragon Gene Therapy, a unit of Catalent Biologics, for clinical manufacturing capabilities and capacity for multiple active preclinical lysosomal disorder programs that are currently in development in collaboration with the University of Pennsylvania. [Amicus Therapeutics, Inc.] Press Release

OncoSec Receives Exclusive Licensing Rights from Dana-Farber Cancer Institute to CAR T-Cell Therapies for the Treatment of Solid Tumor Cancers

OncoSec Medical Incorporated announced that it has entered into a collaboration with Dana-Farber Cancer Institute and The Marasco Laboratory to develop CAR T-cell therapies for triple-negative breast cancer and other solid tumor cancers. [OncoSec Medical Incorporated] Press Release

Seelos Therapeutics Announces Acquisition of an Exclusive Worldwide License of Gene Therapy Program to Address Parkinson’s Disease from Duke University

Seelos Therapeutics, Inc. announced the exclusive worldwide licensing of a gene therapy program targeting the regulation of the SNCA gene, which encodes alpha-synuclein expression, from Duke University. Seelos plans to study this approach, named SLS-004, initially in Parkinson’s Disease. [Seelos Therapeutics, Inc.] Press Release

Humanigen Secures Exclusive Worldwide License to Gene-Editing Technology from Mayo Clinic to Improve CAR-T

Humanigen, Inc. announced that it has entered into an exclusive worldwide license with the Mayo Clinic to certain technologies used to create CAR-T cells lacking GM-CSF expression through various gene-editing tools including CRISPR-Cas9. [Humanigen, Inc.] Press Release

Vycellix Founders Awarded Major Swedish Grant to Establish NEXTGEN-NK

Vycellix^™, Inc. announced that the company has been included as a collaborative partner in the new Competence Center for Next-Generation NK Cell-based Cancer Immunotherapy being established at Karolinska Institutet, Stockholm, Sweden. [Vycellix^™] Press Release

Third Clinical Site Initiated for BrainStorm Cell Therapeutic’s Phase II Progressive MS Study

BrainStorm Cell Therapeutics Inc. announced that the company has contracted with the Keck School of Medicine of The University of Southern California (USC) and its academic medical center, Keck Medicine of USC as the third clinical study site for the company’s Phase II open-label, multicenter study of repeated intrathecal administration of autologous MSC-NTF cells in participants with progressive Multiple Sclerosis (MS). [BrainStorm Cell Therapeutics Inc.] Press Release

Minovia Announces Dosing of Patient in First Mitochondrial Cell Therapy Trial for the Treatment of Pearson Syndrome

Minovia Therapeutics announced dosing of the first patient in a Phase I/II clinical trial of the company’s Mitochondrial Augmentation Therapy for the treatment of Pearson syndrome. [Minovia Therapeutics] Press Release

Arrowhead Pharmaceuticals Receives Fast Track Designation for ARO-AAT for Treatment of Alpha-1 Liver Disease

Arrowhead Pharmaceuticals Inc. announced that the FDA has granted Fast Track designation to ARO-AAT, the company’s second generation subcutaneously RNAi. [Arrowhead Pharmaceuticals Inc.] Press Release

Mexican President Eases Up on Researchers’ Travel Rules

A month after announcing increased austerity measures on international travel for scientists, Mexico’s National Council of Science and Technology announced that at least one restriction would be loosened. Scientists would not require presidential approval for every trip abroad. [The Scientist] Editorial

Stem Cell Funding Agency CIRM Is Nearly Out of Funds

After funding stem cell research since 2004, the California Institute for Regenerative Medicine (CIRM) is running out of funds. The state agency currently has funding requests for $88 million pending but only $33 million left to give out to scientists. [The Scientist] Editorial

Hungarian Government Takes Control of Research Institutes despite Outcry

After months of struggle between Hungary’s research ministry and its scientific community, the nation’s parliament ratified a law on 2 July that gives the government control over the 40 or so institutes belonging to the Hungarian Academy of Sciences. The government says that its aim is to make research more innovative. [Nature News] Editorial

MHRA

EAMS Scientific Opinion: Polatuzumab Vedotin in Combination with Bendamustine and Rituximab for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Adult Patients Who Are Not Eligible for Hematopoietic Stem Cell Transplant Notice

TGA

Australian Regulatory Guidelines for Biologicals Notice

NEW 5^th Annual Cell & Gene Therapy Congress
October 24-25, 2019
London, United Kingdom

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Position – Translational Gene Therapy (Fred Hutchinson Cancer Research Center)

Senior Scientist – Immuno-Oncology of Hematologic Malignancies (University of Kansas School of Medicine)

Research Scientist – Cellular Electrophysiology (Duke University)

Stem Cell Podcast Co-Host (Stem Cell Podcast)

Postdoctoral Scientist – Computational Biologist (Cedars-Sinai Medical Center)

Senior Scientist – Antigen Presentation (Astellas Pharma)

Postdoctoral Research Fellowships – Kidney Disease (Vanderbilt University Medical Center)

Postdoctoral Scholarship – Gene Therapy for Osteopetrosis (Lund University)

Postdoctoral Fellow – Single Cell Genomics (BC Cancer Research Center)

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

Postdoctoral Fellowship – Natural Killer Cells, Cancer and Immunotherapy (Dalhousie University)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Cell Therapy News? Click here to submit!

Comments or suggestions? Submit your feedback here.