Mutant RAS neoantigen epitopes (RAS neoantigens)

Mutant RAS neoantigen epitopes are short peptide sequences derived from oncogenic mutations in the RAS GTPase family (primarily KRAS, NRAS, and HRAS) that are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules. These mutations, most commonly occurring at codons 12, 13, and 61, create novel amino acid sequences that the immune system can recognize as foreign (non-self). Because these mutations are highly prevalent in aggressive malignancies such as pancreatic, colorectal, and lung cancers, and are absent in healthy tissues, they represent high-quality targets for immunotherapy. (Source: Nature, 2022, doi:10.1038/s41586-022-04485-1; Frontiers in Immunology, 2021, doi:10.3389/fimmu.2021.665045). Therapeutic approaches targeting these epitopes include cancer vaccines (mRNA, peptide, or viral vectors) designed to prime the patient's own T cells, and adoptive cell therapies such as TCR-engineered T cells (TCR-T) that are pre-programmed to recognize specific RAS-peptide-HLA complexes. Unlike small molecule inhibitors that bind directly to the RAS protein, neoantigen-directed therapies rely on the cellular machinery to display the target, offering a way to address RAS variants that have historically been considered undruggable. The efficacy of these treatments is highly dependent on the patient's specific HLA allele, as the MHC molecule must be capable of binding and presenting the mutant peptide to T cells. (Source: Journal of Hematology & Oncology, 2024, doi:10.1186/s13045-024-01532-2; ClinicalTrials.gov).

Other names

Mutant RAS-derived neoepitopesKRAS/NRAS/HRAS mutant peptidesRAS-derived peptide-MHC complexesMutant RAS tumor-specific antigens

Induction of neoantigen-specific cytotoxic T-lymphocyte response; TCR-mediated recognition of peptide-HLA complexes on tumor cells.