KRAS mutant neoantigen peptide-MHC class I complex (KRAS-neoantigen-MHC-I)

KRAS mutant neoantigen peptides presented by MHC class I molecules are tumor-specific antigens (TSAs) that arise from somatic mutations in the KRAS gene, a key driver in many human malignancies (Simanshu et al., 2017, Cell [https://doi.org/10.1016/j.cell.2017.08.010]). These mutations, most commonly occurring at codons 12, 13, or 61, result in the production of altered proteins that are processed into short peptides and displayed on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (Yarchoan et al., 2017, Nat Rev Cancer [https://doi.org/10.1038/nrc.2017.11]). This presentation allows the immune system, specifically CD8+ T cells, to distinguish malignant cells from healthy ones, as these mutant sequences are not present in the normal proteome. Consequently, these complexes are prime targets for precision immunotherapies such as T-cell receptor (TCR) engineered T-cell therapy, neoantigen vaccines, and bispecific T-cell engagers (Leidner et al., 2022, NEJM [https://doi.org/10.1056/NEJMoa2119662]). Targeting these pMHC complexes aims to induce a potent and selective anti-tumor immune response while sparing normal tissues that express only wild-type KRAS (Pant et al., 2024, Nat Med [https://doi.org/10.1038/s41591-023-02760-3]).

Other names

KRAS mutant peptide-HLA complexKRAS neoepitope-MHC complexKRAS-mutant pHLAKRAS-mutant pMHCKRAS neoantigen-HLA-I complex

T-cell receptor (TCR) mediated recognition and subsequent immune-mediated lysis of tumor cells (Leidner et al., 2022, NEJM [https://doi.org/10.1056/NEJMoa2119662]).