Treatment of acute lymphoblastic leukaemia with the second generation of CD 19 CAR ‐T containing either CD 28 or 4‐1 BB

作者：Shiqi Li, Jiasi Zhang, Meiling Wang, Gang Fu, Yunyan Li, Pei Li, Zhouxing Xiong, Dabing Qin, Rui Zhang, Xiaobo Tian, Zhihao Wei, Run Chen, Xuejiao Chen, Jia Wan, Jun Chen, Jun Chen, Xia Wei, Yanmin Xu, Pei Zhang, Ping Wang, Xi Peng, Sainan Yang, Junjie Shen, Zhi Yang, Jieping Chen, Jieping Chen, Cheng Qian · 发表于：British Journal of Haematology · 年份：2018 · DOI：10.1111/bjh.15195 · 被引用次数：76 · 研究领域：CAR-T cell therapy research、Advancements in Semiconductor Devices and Circuit Design、Integrated Circuits and Semiconductor Failure Analysis

T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia (ALL). However, the difference between CD28 and 4-1BB costimulatory signalling in CAR-T treatment has not been well elucidated in clinical trials. In this study, we treated 10 relapsed or refractory ALL patients with the second generation CD19 CAR-T. The first 5 patients were treated with CD28-CAR and the other 5 patients were treated with 4-1BB CAR-T. All the 10 patients were response-evaluable. Three patients achieved complete remission and 1 patient with extramedullary disease achieved partial response after CD28-CAR-T treatment. In the 4-1BB CAR-T treatment group, 3 patients achieved complete remission. Furthermore, FLT-3 ligand (FLT3LG) was highly correlated with response time and may serve as a prognosis factor. No severe adverse events were observed in these 10 treated patients. Our study showed that both CD28 CAR-T and 4-1BB CAR-T both worked for response but they differed in response pattern (peak reaction time, reaction lasting time and reaction degree), adverse events, cytokine secretion and immune-suppressive factor level.