Engineering Novel CD19/CD22 Dual-Target CAR-T Cells for Improved Anti-Tumor Activity
Wanying Zeng, Qing Zhang, Yangmin Zhu, Ruiming Ou, Liang Peng, Baolei Wang, Huijuan Shen, Zhi Liu, Lisheng Lü, Pumin Zhang, Shuang Liu
Abstract
Despite high remission rates following chimeric antigen receptor T cell (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL), relapse due to loss of the targeted antigen is increasingly recognized as a mechanism of immune escape. We hypothesized that simultaneous targeting of CD19 and CD22 may improve the CAR-T effect. The in vitro and in vivo leukemia model was established, and the anti-tumor effects of BiCAR-T, CD19 CAR-T, CD22 CAR-T, and LoopCAR6 cells were observed. We found that the BiCAR-T cells showed significant cytotoxicity in vitro and in vivo. The CD19/CD22 bivalent CAR provides an opportunity to test whether simultaneous targeting may reduce the risk of antigen loss.