Gu Xinyu, Zhang Yalan, Zhou Weilin, Wang Fengling, Yan Feiyang, Gao Haozhan, Wang Wei
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, People's Republic of China.
Exp Hematol Oncol. 2024 Jul 26;13(1):70. doi: 10.1186/s40164-024-00542-2.
Chimeric antigen receptor (CAR) T-cell therapy has achieved substantial clinical outcomes for tumors, especially for hematological malignancies. However, extending the duration of remission, reduction of relapse for hematological malignancies and improvement of the anti-tumor efficacy for solid tumors are challenges for CAR-T cells immunotherapy. Besides the endeavors to enhance the functionality of CAR-T cell per se, optimization of the infusion and delivery strategies facilitates the breakthrough of the hurdles that limited the efficacy of this cancer immunotherapy. Here, we summarized the infusion and delivery strategies of CAR-T cell therapies under pre-clinical study, clinical trials and on-market status, through which the improvements of safety and efficacy for hematological and solid tumors were analyzed. Of note, novel infusion and delivery strategies, including local-regional infusion, biomaterials bearing the CAR-T cells and multiple infusion technique, overcome many limitations of CAR-T cell therapy. This review provides hints to determine infusion and delivery strategies of CAR-T cell cancer immunotherapy to maximize clinical benefits.
嵌合抗原受体（CAR）T细胞疗法已在肿瘤治疗中取得了显著的临床成效，尤其是在血液系统恶性肿瘤方面。然而，延长缓解期、降低血液系统恶性肿瘤的复发率以及提高实体瘤的抗肿瘤疗效，是CAR-T细胞免疫疗法面临的挑战。除了致力于增强CAR-T细胞本身的功能外，优化输注和递送策略有助于突破限制这种癌症免疫疗法疗效的障碍。在此，我们总结了临床前研究、临床试验及上市状态下CAR-T细胞疗法的输注和递送策略，并分析了其对血液系统肿瘤和实体瘤安全性及疗效的改善情况。值得注意的是，新型输注和递送策略，包括局部区域输注、负载CAR-T细胞的生物材料以及多次输注技术，克服了CAR-T细胞疗法的许多局限性。本综述为确定CAR-T细胞癌症免疫疗法的输注和递送策略以实现临床效益最大化提供了思路。
