Mutant Kirsten rat sarcoma virus oncogene homolog (KRAS) neoantigen (Mutant KRAS)

Mutant KRAS neoantigens are highly specific tumor antigens derived from somatic mutations in the KRAS gene, most commonly at the G12, G13, or Q61 positions [Simanshu et al., 2017]. These mutations result in the presentation of novel peptide sequences by Human Leukocyte Antigen (HLA) molecules on the surface of cancer cells, which can be recognized by the immune system as non-self [Tran et al., 2016]. T-cell responses directed against these neoantigens are a major focus of modern immunotherapy, particularly through the use of adoptive cell transfer (ACT) and T-cell receptor (TCR) gene therapy [Leidner et al., 2022]. In diseases like pancreatic, colorectal, and lung cancers, KRAS mutations act as primary oncogenic drivers, making the resulting neoantigens stable and ubiquitous targets within the tumor [Bear et al., 2020]. Unlike wild-type KRAS, these mutant neoantigens are not expressed in healthy tissues, significantly reducing the risk of on-target, off-tumor toxicity. Therapeutic strategies aim to harness or engineer T cells to specifically bind these peptide-HLA complexes, triggering a potent cytotoxic response against the malignancy [Elicio Therapeutics, 2024].

Other names

KRAS neoepitopeMutant KRAS peptide-HLA complexKRAS G12D neoantigenKRAS G12V neoantigenKRAS G12R neoantigen

T-cell receptor (TCR) mediated recognition of mutant peptide-HLA complexes leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.