KRAS-derived neoantigen peptide–HLA-A*02:01 complex (KRAS-HLA-A*02:01)

The KRAS-derived neoantigen peptide–HLA-A*02:01 complex is a molecular assembly consisting of a mutated KRAS peptide fragment bound to the human leukocyte antigen (HLA) allele A*02:01 (Waters & Der, 2018; Bear et al., 2021). KRAS is one of the most frequently mutated oncogenes in human cancers, particularly in pancreatic, colorectal, and lung adenocarcinomas (Simanshu et al., 2017). When these mutations (such as G12D, G12V, or G12C) occur, the resulting neoantigenic peptides can be processed and presented on the cell surface by MHC Class I molecules like HLA-A*02:01 (Bear et al., 2021). This complex serves as a highly specific target for the immune system because it is absent in healthy tissues, making it an ideal candidate for precision immunotherapy (Leidner et al., 2022). Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cell therapies, bispecific T-cell engagers, and neoantigen vaccines like ELI-002 (Leidner et al., 2022; Elicio Therapeutics). By specifically recognizing this peptide-MHC (pMHC) complex, these therapies aim to induce T-cell mediated destruction of tumor cells while sparing normal cells. However, challenges such as HLA downregulation by tumors and the requirement for specific patient HLA genotypes remain significant hurdles in clinical application (Leidner et al., 2022).

Other names

KRAS neoantigen-MHC complexKRAS-mutant peptide-HLA-A*02:01pMHC complex (KRAS)KRAS G12D-HLA-A*02:01 complexKRAS G12V-HLA-A*02:01 complex

Binding of T-cell receptors (TCRs) or TCR-mimetic antibodies to the peptide-MHC complex to trigger T-cell mediated cytotoxicity against tumor cells.