Cell Therapy News Volume 21.04 | Feb 3 2020

TOP STORY

Interleukin-23 Engineering Improves CAR T Cell Function in Solid Tumors

Investigators found that, upon T cell antigen receptor stimulation, T cells up-regulated the interleukin (IL)-23 receptor and the IL-23α p19 subunit, but not the p40 subunit. They engineered expression of the p40 subunit in T cells and obtained selective proliferative activity in activated T cells via autocrine IL-23 signaling. [Nat Biotechnol] Abstract

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A Computationally Designed Chimeric Antigen Receptor Provides a Small-Molecule Safety Switch for T-Cell Therapy

To improve the safety of CAR-T-cell therapy, investigators computationally designed a chemically disruptable heterodimer (CDH) based on the binding of two human proteins. The CDH self-assembly could be disrupted by a small-molecule drug and had a high-affinity protein interface with minimal amino acid deviation from wild-type human proteins. [Nat Biotechnol] Abstract

Decellularized Tissue Engineered Hyaline Cartilage Graft for Articular Cartilage Repair

By combining the advantages of cartilage tissue engineering and decellularization technology, researchers developed a decellularized allogeneic hyaline cartilage graft, named dLhCG, which achieved superior efficacy in articular cartilage repair and surpassed living autologous chondrocyte-based cartilaginous engraftment and autologous chondrocyte implantation. [Biomaterials] Abstract

Control of Metastases via Myeloid CD39 and NK Cell Effector Function

Using conditional Cd39 gene-targeted mouse strains and adoptive NK cell transfers, scientists showed that CD39 expressed on bone marrow-derived myeloid cells was essential for anti-CD39’s anti-metastatic activity, but NK cell expression of CD39 was not critical. [Cancer Immunol Res] Abstract

Insulin-Deficient Diabetic Condition Upregulates Insulin Secreting Capacity of Human iPSC-Derived Pancreatic Endocrine Progenitor Cells after Implantation in Mice

The authors investigated the effect of insulin-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell-derived pancreatic endocrine progenitor cells, which contained a high proportion of chromogranin A⁺ NK6 homeobox 1⁺ cells while very few insulin⁺ cells, were used. [Diabetes] Abstract

Ascorbate and Iron Are Required for the Specification and Long-Term Self-Renewal of Human Skeletal Mesenchymal Stromal Cells

Researchers found that one of the histone demethylases affected by ascorbate, KDM4B, was necessary to promote the specification of human pluripotent stem cells (hPSC)-mesenchymal stem cells (MSCs). This mechanistic understanding led to the metabolic optimization of hPSC-MSCs with an extended lifespan in vitro and the ability to fully repair cartilage defects upon transplantation in vivo. [Stem Cell Reports] Full Article

Pulsed Electromagnetic Fields Promote Repair of Focal Articular Cartilage Defects with Engineered Osteochondral Constructs

Following in vitro optimization, the potential clinical translation of pulsed electromagnetic fields was evaluated in a preliminary in vivo pre-clinical adult canine model. Engineered osteochondral constructs were cultured to maturity and implanted into focal defects created in the stifle joint. [Biotechnol Bioeng] Abstract

Prolongation of Rat-to-Mouse Islets Xenograft Survival by Co-Transplantation of Autologous IL-10 Differentiated Murine Tolerogenic Dendritic Cells

Tolerogenic dendritic cells (DCs) were generated by differentiating bone marrow cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin (IL)-10. The phenotype of IL-10 DCs wertr characterized in vitro by expression of costimulatory/inhibitory molecules and cytokines, their function by phagocytosis and T-cell stimulation assays. [Xenotransplantation] Abstract

Characterization of an Anti-CD5 Directed CAR T-Cell against T-Cell Malignancies

To extensively explore and investigate the biological properties of a CD5 CAR, scientists evaluated multiple CD5 CAR constructs and constructed three murine models to characterize the properties of CD5 down-regulation, the efficacy and specificity produced by different CD5 CAR construct designs, and the impact of incorporating a CD52 safety switch using CAMPATH to modulate the persistency and function of CAR cells. [Stem Cell Rev Rep] Abstract

Correlation Between the Efficacy of Stem Cell Therapy for Osteonecrosis of the Femoral Head and Cell Viability

A total of 30 patients with idiopathic osteonecrosis of the femoral head underwent core decompression combined with autologous stem cell transplantation. The Harris hip score and difference in necrosis area before and after surgery were measured. The mean repair ratio was set as the threshold to divide the patients into group A and group B. [BMC Musculoskelet Disord] Full Article

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Enhancing Cancer Immunotherapy with Nanomedicine

The authors discuss how nanomedicine-based treatment strategies are well suited to immunotherapy on the basis of nanomaterials’ ability to direct immunomodulators to tumors and lymphoid organs, to alter the way biologics engage with target immune cells and to accumulate in myeloid cells in tumors and systemic compartments. [Nat Rev Immunol] Abstract

Rabbit ATG/ATLG in Preventing Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation: Consensus-Based Recommendations by an International Expert Panel

Fourteen clinically relevant key questions to the domains indication, administration, and post-transplant management were developed and recommendations were produced using the Delphi technique involving a Panel of 14 experts. Antithymocyte globulinATG/anti-T lymphocyte globulin (ATLG) was strongly recommended as part of myeloablative conditioning regimen prior to matched or mismatched unrelated bone marrow or peripheral blood allogeneic hematopoietic stem cell transplantation in malignant diseases to prevent severe acute and chronic graft-versus-host disease. [Bone Marrow Transplant] Abstract

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SQZ Biotech Announces First Patient Dosed in Phase I Trial of SQZ-PBMC-HPV for HPV⁺ Tumors

SQZ Biotechnologies (SQZ) announced that the first patient in its Phase I clinical trial of SQZ-PBMC-HPV has received their first dose. SQZ-PBMC-HPV is an autologous cell therapy candidate comprised of SQZ-engineered antigen presenting cells designed to induce CD8 T cell responses against HPV16. [SQZ Biotechnologies] Press Release

Rubius Therapeutics Announces First Patient Dosed in Phase Ib Trial of RTX-134 for the Treatment of Patients with Phenylketonuria

Rubius Therapeutics, Inc. announced that the first patient has been dosed in its Phase Ib trial of RTX-134, an allogeneic, off-the-shelf cellular therapy for the potential treatment of patients with phenylketonuria [Rubius Therapeutics] Press Release

BrainStorm Receives Notice of Intention to Grant Additional EU patent for NurOwn^®

BrainStorm Cell Therapeutics Inc. announced that the European Patent Office has communicated its intention to grant a European patent titled ‘Methods of Generating Mesenchymal Stem Cells which Secrete Neurotrophic Factors‘. Allowed claims cover the method for manufacturing MSC-NTF cells. [BrainStorm Cell Therapeutics Inc.] Press Release

US Prosecutor Leading China Probe Explains Effort That Led to Charges against Harvard Chemist

The US government isn’t prosecuting Charles Lieber because he’s a world-renowned inorganic chemist at Harvard University, says the US attorney who last week drew headlines by charging Lieber with making false statements about his ties to Chinese research institutions. Nor does the Department of Justice think for one minute that Lieber is a spy. [ScienceInsider] Editorial

Cash from Cannabis Companies Creates Conflicted Researchers

Imagine that scientists charged with doing research on tobacco’s health implications were funded by tobacco companies. In fact, the tobacco industry used this tactic for decades to cast doubt on the adverse health effects of smoking. But today it would be an outrageous conflict of interest – research on addictive drugs shouldn’t be paid for by people who stand to profit from selling them. Yet this is exactly what is happening with cannabis. [STAT News] Editorial

Chan Zuckerberg Initiative to Fund 30 Patient Groups, Aiming to Build a Model for Tackling Rare Diseases

On January 3^rd, Mark Zuckerberg and his spouse Dr. Priscilla Chan’s philanthropic vehicle announced a set of grants that executives there hope will create a model for tackling any rare disease: financing patient-led groups, and giving them training and resources. [STAT News] Editorial

FDA

Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations (FDA-2019-D-5392) Notice

NEW Gene- and Cell-Based Therapies: CRISPR, Stem Cells, and Beyond
March 2-4, 2020
San Francisco, California, United States

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NEW Postdoctoral Fellow – Inflammation and Cancer (University Hospital of Erlangen)

Lecturer – Clinical Pharmacology (University of Bristol)

Research Assistant – Organoid Modeling for Stem Cell Therapies (Boston Children’s Hospital)

Research Fellow – Regenerative Medicine (University of Edinburgh)

Postdoctoral Researcher – Drug Delivery (University of Minnesota Twin Cities)

Postdoctoral Researchers – Cell Biology (Medicinal Bioconvergence Research Center)

Postdoctoral Scientist – Functional Pharmacology (Genentech, Inc.)

Postdoctoral Fellow – Cancer Research (BC Cancer)

Research Assistant – Cancer Research (BC Cancer)

Postdoctoral Fellow – Single Cell Genomics (BC Cancer)

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