Zhang, ShangkunGu, ChaojiangHuang, LifangWu, HanShi, JiangzhouZhang, ZijianZhou, YongZhou, JingjiaoGao, YangLiu, JiaxingLeng, YingqiLiu, XiyuZhang, QinxingHuang, LiangTong, XiqinYoung, Ken HLi, JiapengZhu, HaichuanZhang, Tongcun2022-07-012022-07-012022-06-212045-23222045-2322https://hdl.handle.net/10161/25444CAR 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.T-LymphocytesHumansHodgkin DiseaseAntibodiesImmunotherapy, AdoptiveLymphoma, Large-Cell, AnaplasticKi-1 AntigenJournal article2022-07-01