肿瘤细胞治疗研究
英文原题：Tandem CAR-T cells targeting MUC1 and PSCA combined with anti-PD-1 antibody exhibit potent preclinical activity against non-small cell lung cancer.
嵌合抗原受体（CAR）-T 细胞在治疗实体瘤时面临诸多问题，包括肿瘤抗原异质性和免疫抑制。
嵌合抗原受体（CAR）T 细胞在治疗实体瘤时面临多项问题，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 PD-1，可能解决这些问题并增强 CAR-T 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。本研究构建了一种二价串联 CAR-T（Tan CAR-T），可同时靶向 MUC1 和 PSCA，并在体外和体内评估其抑制 NSCLC 的效果。结果显示，与单靶点 CAR-T 相比，Tan CAR-T 的肿瘤杀伤效果更强；联合抗 PD-1 抗体后，其抗肿瘤疗效可进一步增强。本研究报告了此前未被研究过的 Tan CAR-T 治疗 NSCLC 的效果，为抗 PD-1 抗体联合靶向 MUC1 和 PSCA 的 Tan CAR-T 治疗 NSCLC 提供临床前依据。
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.
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