Scholarlink

<p>Claudin18 isoform 2 (CLDN18.2), primarily expressed in gastric tissue and upregulated in pancreatic cancer (PC), is a key target for innovative treatments like chimeric antigen receptor T (CAR-T) cell therapy. However, CAR-T’s effectiveness comes with a significant risk of on-target, off-tumor (OTOT) toxicity due to CLDN18.2’s presence in normal gastric mucosa. To address this, we developed CLDN18.2-specific synthetic T cell receptor and antigen receptor T (STAR-T) cells. Our research shows that STAR-T and CAR-T cells have comparable in vitro cytotoxicity, but STAR-T cells cause less gastric damage in vivo despite having weaker antitumor effects than CAR-T cells. Clinical tests with gastroscopes confirmed the gastric safety of STAR-T cell therapy, which effectively controlled the disease. Additionally, incorporating the IL12β p40 subunit into STAR-T cells enhanced their function in both lab and animal studies. This evidence suggests that CLDN18.2 STAR-T cell could be a safer alternative to CAR-T cell therapy for PC, meriting further clinical trials.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

CLDN18.2-targeting STAR-T cell therapy for pancreatic cancer: a strategy to minimize gastric off-tumor toxicity compared to CLDN18.2 CAR-T

  • 期刊论文

  • 发表日期：

    2025年4月29日

查看全文
  • Wei Zhang,
  • Miao Zeng,
  • Xingyu Ma,
  • Jinghong Chen,
  • Jingqiao Qiao,
  • Ziqian He,
  • Guocheng Zhong,
  • Yisheng Li,
  • Li Yu

摘要

Claudin18 isoform 2 (CLDN18.2), primarily expressed in gastric tissue and upregulated in pancreatic cancer (PC), is a key target for innovative treatments like chimeric antigen receptor T (CAR-T) cell therapy. However, CAR-T’s effectiveness comes with a significant risk of on-target, off-tumor (OTOT) toxicity due to CLDN18.2’s presence in normal gastric mucosa. To address this, we developed CLDN18.2-specific synthetic T cell receptor and antigen receptor T (STAR-T) cells. Our research shows that STAR-T and CAR-T cells have comparable in vitro cytotoxicity, but STAR-T cells cause less gastric damage in vivo despite having weaker antitumor effects than CAR-T cells. Clinical tests with gastroscopes confirmed the gastric safety of STAR-T cell therapy, which effectively controlled the disease. Additionally, incorporating the IL12β p40 subunit into STAR-T cells enhanced their function in both lab and animal studies. This evidence suggests that CLDN18.2 STAR-T cell could be a safer alternative to CAR-T cell therapy for PC, meriting further clinical trials.