Wang Aying, Lv Tangfeng, Song Yong
The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
Cell Immunol. 2023 Sep-Oct;391-392:104760. doi: 10.1016/j.cellimm.2023.104760. Epub 2023 Aug 29.
Chimeric antigen receptor (CAR)-T cells encounter many issues when treating solid tumors, including tumor antigen heterogeneity and immunosuppression. United targeting of two tumor-associated antigens (TAAs) and blocking of PD-1 may solve this problem and enhance the function of CAR-T. Mucin 1 (MUC1) and prostate stem cell antigen (PSCA) are overexpressed in non-small cell lung cancer (NSCLC). Here, we constructed a bivalent tandem CAR-T (Tan CAR-T), which can simultaneously target MUC1 and PSCA and evaluated its effects of inhibiting non-small cell lung cancer (NSCLC) in vitro and in vivo. Results indicated that the tumor killing effect of these Tan CAR-T was more effective than that of single-target CAR-T, its antitumor efficacy could be further strengthened by anti-PD-1 antibody. Our study reported a previously unstudied therapeutic effect of a Tan CAR-T in NSCLC, providing a preclinical rationale for anti-PD-1 antibody combined with Tan CAR-T targeting MUC1 and PSCA in the treatment of NSCLC.
嵌合抗原受体（CAR）-T细胞在治疗实体瘤时面临许多问题，包括肿瘤抗原异质性和免疫抑制。联合靶向两种肿瘤相关抗原（TAA）并阻断程序性死亡受体1（PD-1）可能解决这一问题并增强CAR-T细胞的功能。黏蛋白1（MUC1）和前列腺干细胞抗原（PSCA）在非小细胞肺癌（NSCLC）中过表达。在此，我们构建了一种双价串联CAR-T细胞（Tan CAR-T），其可同时靶向MUC1和PSCA，并评估了其在体外和体内抑制非小细胞肺癌（NSCLC）的效果。结果表明，这些Tan CAR-T细胞的肿瘤杀伤作用比单靶点CAR-T细胞更有效，抗PD-1抗体可进一步增强其抗肿瘤疗效。我们的研究报道了Tan CAR-T细胞在NSCLC中一种此前未被研究的治疗效果，为抗PD-1抗体联合靶向MUC1和PSCA的Tan CAR-T细胞治疗NSCLC提供了临床前理论依据。
