嵌合抗原受体
T细胞
癌症研究
抗原
细胞毒性T细胞
白血病
白细胞介素21
CD28
免疫学
自然杀伤性T细胞
医学
生物
免疫系统
体外
生物化学
作者
Nai-Shan Zheng,Xiangyu Zhao,Wei Ding,Jinlin Miao,Ze-Kun Liu,Yu‐Le Yong,Renyu Zhang,Yixiao Guo,Lin He,Bin Wang,Xiuxuan Sun,Hengli Yang,Tianjiao Zhang,Qian He,Xiaomin Li,Hai Zhang,Rong Hou,Lin Peng,Ying-Ming Xu,Xiao‐Jun Huang,Zhi‐Nan Chen,Huijie Bian
出处
期刊:Cancer Letters
[Elsevier]
日期:2022-08-01
卷期号:542: 215762-215762
被引量:3
标识
DOI:10.1016/j.canlet.2022.215762
摘要
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.
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