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.
基金：
National Science and Technology Major Project [2017ZX10202102-007]; Ministry of Science and Technology of the People's Republic of China-Key Program for International S&T Cooperation Projects of China at Wuhan University of Science and Technology [2017YFE0129100]; Wuhan Science and Technology Plan Project [2019030703011533]; Postdoctoral Science Foundation of China [2020M682491]; National Natural Science Foundation of China [82100193]; Wuhan former funded science and technology program [2020020602012111]; department of Science and Technology of Hubei Province [2020BCB048]
第一作者单位：[1]Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China
通讯作者：
通讯机构：[1]Wuhan Univ Sci & Technol, Coll Life & Hlth Sci, Inst Biol & Med, Wuhan 430081, Hubei, Peoples R China[5]Tianjin Univ Sci & Technol, Coll Biotechnol, Tianjin Key Lab Ind Microbiol, Key Lab Ind Fermentat Microbiol,Minist Educ, Tianjin 300457, Peoples R China
推荐引用方式(GB/T 7714)：
Zhang Shangkun,Gu Chaojiang,Huang Lifang,et al.The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity[J].SCIENTIFIC REPORTS.2022,12(1):doi:10.1038/s41598-022-14523-0.
APA：
Zhang, Shangkun,Gu, Chaojiang,Huang, Lifang,Wu, Han,Shi, Jiangzhou...&Zhang, Tongcun.(2022).The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity.SCIENTIFIC REPORTS,12,(1)
MLA：
Zhang, Shangkun,et al."The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity".SCIENTIFIC REPORTS 12..1(2022)
