Webinar: Memory-rich CAR-T cell engineering by piggyBac transposon system for solid malignancies

This webinar was broadcasted live on March 30, 2023 through Labroots.

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.

Learning Objectives
  • 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.

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Dr. Shigeki Yagyu

Dr. Shigeki Yagyu, M.D., Ph.D.

Professor, Shinshu University, Innovative Research & Liaison Organization

Shigeki Yagyu is a Pediatric Oncologist and Professor at Shinshu University in Japan. Shigeki heads a basic and translational research laboratory focused on developing novel cell, and gene therapy approaches for hematologic and solid malignancies. In particular, he is interested in the clinical application of cellular immunotherapy, including CAR-T and NK cells. Shigeki previously performed his postdoctoral training at the Center for Cell and Gene therapy at Baylor College of Medicine where he investigated mesenchymal stromal cells and induced pluripotent stem cells for cell therapy. He also holds multiple patents related to diagnostic tools for neuroblastoma, developing novel CAR-T cells, and manufacturing CAR-expressing immune cells.