Mutant RAS-derived peptide-MHC complex (Mutant RAS-pMHC)

Mutant RAS-derived peptides presented on Major Histocompatibility Complex (MHC) molecules represent a critical class of tumor-specific neoantigens (Prior et al., 2020, Cancer Cell). RAS genes, including KRAS, NRAS, and HRAS, are the most frequently mutated oncogenes in human cancers, particularly in pancreatic, colorectal, and lung adenocarcinomas (Simanshu et al., 2017, Cell). Somatic mutations in these genes result in altered protein sequences; these mutant proteins are subsequently processed into peptides and displayed on the cell surface by MHC Class I or Class II molecules (Tran et al., 2016, NEJM). These peptide-MHC (pMHC) complexes are specifically recognized by T-cell receptors (TCRs), which triggers a targeted immune response against the malignant cells while sparing healthy tissue (Wang et al., 2023, Frontiers in Immunology). Because these mutations are highly prevalent and tumor-specific, they are primary targets for advanced immunotherapies such as TCR-engineered T-cell (TCR-T) therapies, neoantigen-based vaccines, and TCR-like bispecific antibodies (Bear et al., 2020, Cancer Immunology Research). Therapeutic development focuses on specific hotspot mutations, such as KRAS G12D or G12V, presented by common HLA alleles to maximize patient eligibility (Moderna, 2024, Clinical Trials).

Other names

Mutant RAS neoantigenRAS-HLA complexKRAS/NRAS/HRAS mutant peptide-MHCOncogenic RAS neoantigenMutant RAS-pMHCMutant RAS-derived peptides presented on MHC class I/II and recognized by T-cell receptors

T-cell receptor (TCR) mediated recognition of mutant peptide-MHC complexes on the tumor cell surface, leading to the formation of an immunological synapse, secretion of cytotoxic granules (perforin/granzyme), and induction of apoptosis in the target cell (Tran et al., 2016, NEJM; Wang et al., 2023, Frontiers in Immunology).