嵌合抗原受体 (CAR) T 细胞疗法在治疗 B 细胞恶性肿瘤方面取得了显着的临床成功。然而，其在实体瘤中的临床疗效有限，主要受到靶抗原异质性的限制。为了克服抗原异质性，我们开发了过度表达 LIGHT 的 CAR T 细胞，LIGHT 是癌细胞上 LTβR 和免疫细胞上 HVEM 的配体。表达 LIGHT 的 CAR T 细胞表现出由 CAR 介导的抗原导向的细胞毒性，以及通过 LIGHT 与癌细胞上的 LTβR 相互作用介导的抗原非依赖性杀伤作用。此外，表达 LIGHT 的 CAR T 细胞具有免疫刺激特性，可以改善细胞的增殖和细胞溶解特性。这些数据表明表达 LIGHT 的 CAR T 细胞可能提供一种消除抗原阴性肿瘤细胞以防止抗原阴性疾病复发的方法。

Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success in the treatment of B-cell malignancies. However, its clinical efficacy in solid tumors is limited, primarily by target antigen heterogeneity. To overcome antigen heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand of both LTβR on cancer cells and HVEM on immune cells. LIGHT-expressing CAR T cells displayed both antigen-directed cytotoxicity mediated by the CAR and antigen-independent killing mediated through the interaction of LIGHT with LTβR on cancer cells. Moreover, CAR T cells expressing LIGHT had immunostimulatory properties that improved the cells' proliferation and cytolytic profile. These data indicate that LIGHT-expressing CAR T cells may provide a way to eliminate antigen-negative tumor cells to prevent antigen-negative disease relapse.