Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei, 430081, China.
Department of Hematology, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan, 430030, China.
Sci Rep. 2022 Jun 21;12(1):10488. doi: 10.1038/s41598-022-14523-0.
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.
嵌合抗原受体 T 细胞疗法在霍奇金淋巴瘤（HL）和间变大细胞淋巴瘤（ALCL）患者中具有良好的耐受性和疗效。然而，即使是具有 CD28（28z）共刺激结构域的第二代抗 CD30 CAR T 细胞也未能达到理想的完全缓解率。在本研究中，我们开发了针对 CD30 的第二代（CD28z）和第三代（CD28BBz）CAR T 细胞，并研究了它们在体外和体内的疗效。CD28z 和 CD28BBz 抗 CD30 CAR T 细胞在扩增、T 细胞亚群分布、T 细胞活性、效应/记忆和耗竭方面相似。然而，我们发现 28BBz 抗 CD30 CAR T 细胞能够长期持续存在，特异性归巢至肿瘤，并在肿瘤异种移植模型中发挥强大的抗肿瘤活性。随后，我们还证明了第三代抗 CD30 CAR T 细胞具有更小的副作用或潜在的致瘤风险。因此，抗 CD30 CAR T 细胞是治疗霍奇金淋巴瘤的一种安全有效的方法。
