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

我们研究了在PDAC中使用T细胞受体(TCR)工程T细胞进行细胞治疗。通过CRISPR/Cas9介导的T细胞工程，从健康供者中分离出非常罕见的针对PDAC新抗原的TCR，并在原代T细胞中重新表达。工程T细胞将使用携带感兴趣突变的PDAC细胞系和有机化合物来评估其在体外和体内的功能。将分析PDAC肿瘤微环境，以进一步提高T细胞协同工程的TCR治疗效果。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，并尝试将第一批T细胞产品临床测试。

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.