Presentation: Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing

This presentation was given during the Japan Genome Engineering Conference (JSGE) June 2023.

Chimeric Antigen Receptor (CAR)-T cell therapies have become an effective therapeutic option for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to viral vector engineered CAR-T cell therapies faces significant challenges to meet clinical needs, in large part due to high cost and long lead times for manufacturing GMP vector. Therefore, moving to a non-viral gene delivery platform for the manufacture of CAR-T cell therapies is a logical next step. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 and double-stranded DNA (dsDNA) via homology-directed repair (HDR), however yields with this approach have been limiting for clinical application. We discuss here a targeted but HDR-independent approach for the manufacture of CAR-T cell therapies.

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Hyatt Balke-Want

Dr. Hyatt Balke-Want

Postdoctoral Fellow

Stanford Center for Cancer, Cell Therapy Stanford Cancer Institute
Stanford University

Hyatt Balke-Want is a Postdoctoral Fellow with Crystal Mackall and Steven Feldman at the Center for Cancer Cell Therapy, Stanford since 2020. Prior to joining Stanford, Hyatt has been a resident in Internal Medicine and Hematology/Oncology with Michael Hallek (University Hospital Cologne) since 2015 and took care of the very first lymphoma patients treated with CAR-T cells in Germany. During his postdoc Hyatt has focused on developing a CRISPR knock-in based platform to manufacture non-viral CAR-T cells with the ultimate goal to increase the accessibility to CAR-T cell therapies for patients.