Abstract
CD19-targeted chimeric antigen receptor therapies (CAR19) have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CAR19-treated patients experienced 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 number of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac, we developed a virus-free cell engineering system, Quantum CART (qCART™), for development and production of multiplex CAR-T therapies. Here, we demonstrated in vitro and in vivo that consistent, robust, and functional CD20/CD19 dual-targeted CAR-T stem cell memory (TSCM) cells can be efficiently manufactured using the qCART™ system for clinical application. qCART™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Competing Interest Statement: S.C.-Y.W. is a founder of GenomeFrontier Therapeutics, Inc., P.S.C., Y.-C. Chen, W.-K.H., J.C.H., J.-C.T., Y.-W.H., Y.-H.K., P.-H.W., and K.-L.K.W. are affiliated with GenomeFrontier Therapeutics, Inc.