肿瘤细胞治疗研究
英文原题：EGFR TKIs suppress MUC1 glycosylation through the PI3K/AKT/SP1/C1GALT1 pathway to enhance TnMUC1 CAR-T efficacy in EGFR-mutant NSCLC.
本研究表明，EGFR TKIs在体外和体内均能增强TnMUC1 CAR-T细胞疗法在EGFR突变NSCLC中的疗效。
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）是 EGFR 突变癌症（非小细胞肺癌 [NSCLC]）的标准一线治疗，客观缓解率（ORR）约为 60%-70%。然而，优化其治疗疗效仍是一项挑战。NSCLC 细胞表达肿瘤特异性低糖基化 Thomsen-nouvelle（Tn）黏蛋白 1（MUC1）抗原，使其成为 TnMUC1 嵌合抗原受体（CAR）-T 细胞治疗的合适靶点。本研究表明，EGFR TKI 在体外和体内均可增强 TnMUC1 CAR-T 细胞治疗对 EGFR 突变 NSCLC 的疗效。EGFR TKI 通过降低 MUC1 糖基化上调 TnMUC1，从而改善 TnMUC1 CAR-T 细胞的识别和细胞毒性。具体而言，EGFR TKI 调控 TnMUC1 相关的糖基转移酶，其中核心1-β1,3-半乳糖基转移酶 1（C1GALT1）被确定为受 EGFR TKI 下调的关键酶，提示 C1GALT1 可作为潜在的治疗靶点。
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for EGFR-mutant cancer (non-small cell lung cancer [NSCLC]), achieving an objective response rate (ORR) of approximately 60%-70%. However, optimizing their therapeutic efficacy remains a challenge. NSCLC cells express the tumor-specific hypoglycosylated Thomsen-nouvelle (Tn) mucin 1 (MUC1) antigen, making them suitable targets for TnMUC1 chimeric antigen receptor (CAR)-T cell therapy. This study shows that EGFR TKIs enhance the efficacy of TnMUC1 CAR-T cell therapy in EGFR-mutant NSCLC, both in vitro and in vivo. EGFR TKIs upregulate TnMUC1 by reducing MUC1 glycosylation, thereby improving TnMUC1 CAR-T cell recognition and cytotoxicity. Specifically, EGFR TKIs modulate TnMUC1-related glycosyltransferases, with core1-beta1,3-galactosyltransferase 1 (C1GALT1) identified as a key enzyme downregulated by EGFR TKIs, suggesting C1GALT1 as a potential therapeutic target.
MEMBER ACCOUNT
登录成功会直接打开下一页。
