Article
作者: Wei, Ding ; Xu, Ying-Ming ; He, Lin ; Wang, Bin ; Yong, Yu-Le ; Liu, Ze-Kun ; Li, Xiao-Min ; Zhang, Ren-Yu ; Hou, Rong ; He, Qian ; Huang, Xiao-Jun ; Zhao, Xiang-Yu ; Lin, Peng ; Sun, Xiu-Xuan ; Zhang, Tian-Jiao ; Zheng, Nai-Shan ; Bian, Huijie ; Zhang, Hai ; Chen, Zhi-Nan ; Guo, Yi-Xiao ; Miao, Jin-Lin ; Yang, Hai-Jiao
T cell acute lymphoblastic leukemia (T-ALL) is invasive and heterogeneous, and existing therapies are sometimes unsuccessful. Chimeric antigen receptor (CAR) T cell therapy is a breakthrough tumor treatment method, particularly for B cell acute lymphoblastic leukemia. We found that CD147 was highly expressed in tumor T cells of T-ALL patients and T cell lymphoma. Therefore, CD147-CAR T cells that contain a humanized single-chain variable fragment targeting human CD147 and a second-generation CAR frame were constructed for treating T-ALL. CD147-CAR T cells were able to maintain a healthy proliferation rate, preserving a subset of CD62L+/CCR7+ memory T cells. CD147-CAR T cells showed a potent anti-tumor activity against human T-ALL cell line and T-ALL blasts, releasing high level of cytokines in the process. However, CD147-CAR T cells exhibited potential safety toward human normal cells and CD147-deficent cells. NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt mice were used to establish a T-ALL xenograft model and CD147-CAR T cells conferred robust protection against T-ALL progression and significantly improved survival in mice. Overall, we found that CD147 is a potential antigen target of CAR T cell therapy for T-ALL.
