The application of chimeric antigen receptor (CAR)-T cell therapy in patients with advanced solid tumors remains a significant challenge. Simultaneously targeting antigen and the solid tumor microenvironment are two major factors that greatly impact CAR-T cell therapy outcomes. In this study, we engineered CAR-T cells to specifically target B7-H3, a protein commonly found in solid human tumors, using a single-chain variable fragment (scFv) derived from an anti-B7-H3 monoclonal antibody. We tested the antitumor activity of B7-H3 CAR-T cells in mouse models with solid human tumors and determined that B7-H3 CAR-T cells exhibited potent antitumor activity against B7-H3+ tumor cells in vitro and in vivo. In addition, PD-1 decoy receptors were engineered to include extracellular PD-1 fused to the intracellular stimulatory domain of either CD28 or IL-7 receptor, respectively, which were then introduced into B7-H3 CAR-T cells. As a result, these newly modified, superior CAR-T cells exhibited more persistent antitumor activity in B7-H3+/B7-H1+ tumors in vivo. Our findings indicate that B7-H3 specific CAR-T cells have the potential to treat multiple types of advanced solid tumors.

中文翻译：

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具有嵌合抗原受体和诱饵 PD-1 受体的 B7-H3 特异性 T 细胞可根除小鼠模型中已建立的人实体瘤。

嵌合抗原受体 (CAR)-T 细胞疗法在晚期实体瘤患者中的应用仍然是一项重大挑战。同时靶向抗原和实体瘤微环境是极大影响 CAR-T 细胞治疗结果的两个主要因素。在这项研究中，我们使用源自抗 B7-H3 单克隆抗体的单链可变片段 (scFv) 设计了 ​​CAR-T 细胞以特异性靶向 B7-H3，这是一种常见于人类实体肿瘤中的蛋白质。我们在人类实体瘤小鼠模型中测试了 B7-H3 CAR-T 细胞的抗肿瘤活性，并确定 B7-H3 CAR-T 细胞在体外和体内对 B7-H3+ 肿瘤细胞表现出有效的抗肿瘤活性。此外，PD-1 诱饵受体被设计为包括细胞外 PD-1，分别与 CD28 或 IL-7 受体的细胞内刺激域融合，然后将其引入 B7-H3 CAR-T 细胞。因此，这些新修饰的优质 CAR-T 细胞在体内 B7-H3+/B7-H1+ 肿瘤中表现出更持久的抗肿瘤活性。我们的研究结果表明，B7-H3 特异性 CAR-T 细胞具有治疗多种晚期实体瘤的潜力。