Scientific Reports (Jun 2022)

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

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

DOI
https://doi.org/10.1038/s41598-022-14523-0
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 12

Abstract

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Abstract 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.