Incongruity between T cell receptor recognition of breast cancer hotspot mutations ESR1 Y537S and D538G following exogenous peptide loading versus endogenous antigen processing.

ABSTRACT: T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across additional cancer types, new TCRs recognizing cancer-specific antigen targets are needed. Driver mutations in AKT1, ESR1, PIK3CA, and TP53 are common in patients with metastatic breast cancer (MBC) and if immunogenic could serve as ideal tumor-specific targets for TCR T therapy to treat this disease. Through IFN-γ ELISpot screening of in vitro expanded neopeptide-stimulated T cell lines from healthy donors and MBC patients, we identified reactivity towards 11 of 13 of the mutations. To identify neopeptide-specific TCRs, we then performed single-cell RNA sequencing of one of the T cell lines followi

SUBMITTER: Shafer P 

PROVIDER: S-EPMC10922969 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature