Kirsten rat sarcoma virus oncogene homolog neoantigen (KRAS neoantigen)

KRAS neoantigens are unique peptides derived from mutated Kirsten rat sarcoma virus oncogene homolog (KRAS) proteins that are processed and presented on the surface of cancer cells by major histocompatibility complex (MHC) molecules (Schumacher & Schreiber, 2015). KRAS is a small GTPase that normally regulates cell signaling pathways like MAPK and PI3K; however, point mutations—most commonly at codons 12, 13, or 61—lead to constitutive activation and oncogenic transformation (Simanshu et al., 2017). Because these mutant sequences are absent in healthy tissues, they serve as highly specific "non-self" targets for the immune system, making them ideal candidates for cancer immunotherapies (Yarchoan et al., 2017). Therapeutic strategies targeting KRAS neoantigens include cancer vaccines such as mRNA-5671 and ELI-002, as well as adoptive T-cell therapies using engineered T-cell receptors (TCR-T) (Leidner et al., 2022; Pant et al., 2024). These approaches aim to bypass the challenges of traditional small-molecule inhibitors by leveraging the precision of the cellular immune response to eliminate KRAS-mutant tumors. The efficacy of these treatments is highly dependent on the patient's specific KRAS mutation and their HLA genotype, which determines whether the neoantigen can be successfully presented to T cells (Bear et al., 2020).

Other names

Mutant KRAS peptideKRAS-derived neoantigenmKRAS neoantigen

Induction of antigen-specific T-cell responses and direct T-cell mediated lysis of tumor cells expressing mutant KRAS peptides on MHC molecules (Leidner et al., 2022).