Neo-epitopes derived from mutated tumor suppressor gene RNF43 as targets for adoptive T cell therapy in pancreatic cancer (P17)

我们研究了T细胞受体（TCR）工程T细胞在PDAC中的细胞治疗。从健康供体中分离出非常罕见的PDAC新抗原特异性TCRs，并通过CRISPR/ cas9介导的T细胞工程在原代T细胞中重新表达。将使用PDAC细胞系和携带感兴趣突变的类器官来评估工程T细胞的体外和体内功能。对PDAC肿瘤微环境进行分析，进一步完善T细胞协同工程TCR治疗。同时，我们将把CRISPR/ cas9介导的T细胞工程技术转化为符合gmp的T细胞制造工艺，并尝试在临床上测试第一个T细胞产品。

We investigate cell therapy with T cell receptor (TCR)-engineered T cells in PDAC. Very rare TCRs specific to PDAC neoantigens are isolated from healthy donors and re-expressed in primary T cells via CRISPR/Cas9-mediated T cell engineering. Engineered T cells will be evaluated for their in vitro and in vivo functionality using PDAC cell lines and organoids carrying the mutations of interest. PDAC tumor microenvironment will be analyzed to further improve TCR therapy by T cell co-engineering. In parallel, we will transfer the CRISPR/Cas9-mediated T cell engineering technology into GMP-compliant processes for T cell manufacturing, and attempt to test first T cell products clinically.