In vitro proteasome processing of neo-splicetopes does not predict their presentation in vivo.

ABSTRACT: Proteasome-catalyzed peptide splicing (PCPS) of cancer-driving antigens could generate attractive neoepitopes to be targeted by T cell receptor (TCR)-based adoptive T cell therapy. Based on a spliced peptide prediction algorithm, TCRs were generated against putative KRAS^G12V- and RAC2^P29L-derived neo-splicetopes with high HLA-A*02:01 binding affinity. TCRs generated in mice with a diverse human TCR repertoire specifically recognized the respective target peptides with high efficacy. However, we failed to detect any neo-splicetope-specific T cell response when testing the in vivo neo-splicetope generation and obtained no experimental evidence that the putative KRAS^G12V- and RAC2^P29L-derived neo-splicetopes were naturally processed and presented. F

SUBMITTER: Willimsky G 

PROVIDER: S-EPMC8154032 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature