"Memory-rich CAR-T cell engineering by piggyBac transposon system for solid malignancies"
Sponsored by: MaxCyte®
Chimeric antigen receptor T cell (CAR-T) therapy is still challenging in targeting solid malignancies. The quality of CAR-T cell products, including T-cell memory signatures and exhaustion-related markers, is critical for the function of CAR-T cell therapies. We have developed novel piggyBac transposon (PB) -based CAR-T cells with favorable characteristics and durable antitumor efficacy against solid malignancies. A GMP-compliant manufacturing process successfully generated all CAR-T cells with sufficient CAR positivity and a predominant population of stem cell memory-like phenotypes. We have also identified that PB-transgenes were preferentially introduced into CD45RA+ peripheral blood mononuclear cells. The stem cell memory-like CAR-T cells with CD45RA/CCR7 positive were preferably enriched during the expansion step, which would be associated with the long-term functionality of PB-CAR-T cells. Indeed, PB-CART cells demonstrated sustained killing activity against tumor cells even in multiple tumor re-challenges in vitro and debulked tumors in vivo. A clinical study of PB CAR-T cells for solid tumors is underway to evaluate their safety and efficacy.
Learn the basic background of CAR-T cell differentiation and exhaustion, and how the characteristics and quality of CAR-T cells determine the antitumor functionality.
Understand the state-of-the-art research on strategies for CAR-T cell therapy to enhance memory function.
Study the characteristics of non-viral gene transfer-mediated CAR-T cells, especially their phenotype and antitumor potential.