1. Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system.
- Author
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Chang, Peter S., Chen, Yi-Chun, Hua, Wei-Kai, Hsu, Jeff C., Tsai, Jui-Cheng, Huang, Yi-Wun, Kao, Yi-Hsin, Wu, Pei-Hua, Wang, Po-Nan, Chang, Yi-Fang, Chang, Ming-Chih, Chang, Yu-Cheng, Jian, Shiou-Ling, Lai, Jiann-Shiun, Lai, Ming-Tain, Yang, Wei-Cheng, Shen, Chia-Ning, Wen, Kuo-Lan Karen, and Wu, Sareina Chiung-Yuan
- Abstract
CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-T
SCM ) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies. [ABSTRACT FROM AUTHOR]- Published
- 2024
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