The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity

作者：Zhang, Shangkun; Gu, Chaojiang; Huang, Lifang; Wu, Han; Shi, Jiangzhou; Zhang, Zijian; Zhou, Yong; Zhou, Jingjiao; Gao, Yang; Liu, Jiaxing; Leng, Yingqi; Liu, Xiyu; Zhang, Qinxing; Huang, Liang; Tong, Xiqin; Young, Ken H.; Li, Jiapeng; Zhu, Haichuan^*; Zhang, Tongcun^*

来源：Scientific Reports, 2022, 12(1): 10488.

DOI：10.1038/s41598-022-14523-0

• CHIMERIC ANTIGEN RECEPTOR
• REFRACTORY HODGKIN LYMPHOMA
• BRENTUXIMAB VEDOTIN
• ADOPTIVE IMMUNOTHERAPY
• THERAPY
• CANCER
• PANCREATITIS
• GENOME

CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.

• 单位
  华中科技大学; 武汉大学