Clinical-scale non-viral gene edited CAR-NK cells for cell therapy

Natural Killer (NK) cells, with their unique innate cytotoxic properties, have become increasingly appealing for off-the-shelf allogeneic cell therapy applications. However, efficient clinical-scale non-viral gene editing of primary NK cells remains challenging.

Dr. Namritha Ravinder from Thermo Fisher Scientific will present clinical manufacturing scale-compatible cell processing and non-viral gene editing data from several innovative Gibco™ Cell Therapy Systems™ instruments, feeder-free NK cell media, gene editing tools, and reagents that can be combined into closed, automatable cell therapy manufacturing systems or integrated into existing workflows. The methods she will review were successfully used for both transient gene expression and anti Meso3 CAR-NK cell generation with up to 25% knock-in efficiency. The resulting CAR-NK cells maintained a good expansion rate and showed enhanced cytotoxicity against target cancer cell lines when compared to unedited NK cells.

Dr. Krishanu “Kris” Saha from the University of Wisconsin will then discuss his lab’s non-viral based NK cell engineering work. Despite the promise of NK cells for allogeneic cell therapy, their efficacy against solid tumors is limited due to the upregulation of NK-inhibitory ligands within the tumor microenvironment. Dr. Saha will share how his team is utilizing a CRISPR Cas9 system to disrupt the KLRC1 gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood. Using a completely virus-free workflow, they have demonstrated the feasibility of manufacturing potent allogeneic KLRC1-GD2-CAR NK cells from healthy donors.

• The potential of CAR-NK cells for cell therapy applications
• Benefits and challenges associated with a non-viral CRISPR gene editing protocol for NK cells
• Innovative developments to support GMP processing, electroporation, and culture of human NK cells for clinical applications

Krishanu Saha

Professor at Wisconsin Institute for Discovery

Dr. Saha is a Professor at the University of Wisconsin in the Department of Biomedical Engineering, and member of the NIH Somatic Cell Genome Editing Consortium. His lab focuses on human cell engineering including CRISPR gene editing and epigenetic reprogramming.

Namritha Ravinder

Director, R&D at Thermo Fisher Scientific

Dr. Ravinder is the Director of Research and Development at Thermo Fisher Scientific. Dr. Ravinder and her team are focused on developing closed automated instrument platforms for cell and gene therapy manufacturing applications including cell processing, gene delivery and cell engineering.

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SPEAKERS

Krishanu Saha

Professor at Wisconsin Institute for Discovery

Namritha Ravinder

Director, R&D at Thermo Fisher Scientific

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