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遇到许多问题，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PD-1可能会解决这个问题并增强CAR-T的功能。粘蛋白 1 (MUC1) 和前列腺干细胞抗原 (PSCA) 在非小细胞肺癌 (NSCLC) 中过度表达。在这里，我们构建了一种二价串联CAR-T（Tan CAR-T），可以同时靶向MUC1和PSCA，并在体外和体内评估其抑制非小细胞肺癌（NSCLC）的效果。结果表明，这些Tan CAR-T的肿瘤杀伤作用比单靶点CAR-T更有效，抗PD-1抗体可以进一步增强其抗肿瘤功效。我们的研究报道了此前未研究过的 Tan CAR-T 在 NSCLC 中的治疗效果，为抗 PD-1 抗体联合靶向 MUC1 和 PSCA 的 Tan CAR-T 治疗 NSCLC 提供了临床前理论依据。