Objective: Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated an unprecedented therapeutic efficacy in hematological malignancies; however, its effectiveness in solid tumors remains elusive. In order to enable CAR-T cells more effective to solid tumors, a inverted chimeric cytokine receptor (ICR) was designed, which is consists of the TGF-β extracellular domain, IL-7 receptor intracellular domain, and co-expression on CAR-T cells.

Materials and Methods: We selected prostate specific membrane antigen (PSMA) as a target for CAR-T cells, constructed corresponding effector cells, and verified the anti-tumor activity of this enhanced PSMA-CAR-T cell by a series of repeated target cell stimulation experiments in vitro and the anti-tumor capabilities by using mice xenograft model in vivo.

Results: In vitro experiments showed that co-expression of ICR could significantly enhance sustained anti-tumor capabilities of PSMA-CAR-T cells. Moreover, in vivo experiments also confirmed that the enhanced PSMA-CAR-T cells exhibited significant superior anti-tumor capabilities and could prolong the survival time in the xenograft and PDX models of prostate cancer.

Conclusions: PSMA-CAR-T cells co-expressing ICR can be envisaged as a new therapeutic strategy for prostate cancer and support the translation of this enhanced approach in the clinical setting.

目的：嵌合抗原受体T（CAR-T）细胞疗法已在血液系统恶性肿瘤中显示出空前的疗效。然而，其在实体瘤中的有效性仍然难以捉摸。为了使CAR-T细胞对实体瘤更有效，设计了一种反向嵌合细胞因子受体（ICR），该受体由TGF-β细胞外结构域，IL-7受体细胞内结构域和在CAR-T细胞上共表达组成T细胞。

材料和方法：我们选择前列腺特异性膜抗原（PSMA）作为CAR-T细胞的靶标，构建相应的效应细胞，并通过一系列重复的靶标细胞验证了这种增强的PSMA-CAR-T细胞的抗肿瘤活性通过使用小鼠异种移植物模型进行体外刺激实验和抗肿瘤能力。

结果：体外实验表明，ICR的共表达可以显着增强PSMA-CAR-T细胞的持续抗肿瘤能力。此外，体内实验还证实增强的PSMA-CAR-T细胞表现出显着的优异抗肿瘤能力，并且可以延长前列腺癌异种移植和PDX模型的存活时间。

结论：共表达ICR的PSMA-CAR-T细胞可被认为是前列腺癌的一种新治疗策略，并支持这种增强方法在临床中的翻译。