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

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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.