Kirsten rat sarcoma virus oncogene homolog neoantigen-derived peptides (KRAS neoantigens)

KRAS neoantigen-derived peptides are short amino acid sequences resulting from somatic mutations in the KRAS gene, such as G12D, G12V, or G12C, which are key drivers in pancreatic, colorectal, and lung cancers (Prior et al., 2020, Cancer Research). These mutant proteins are processed into peptides and presented on the tumor cell surface by Human Leukocyte Antigen (HLA) molecules, making them distinct from wild-type KRAS and ideal targets for the immune system (Bear et al., 2021, Cancer Cell). Because these neoantigens are absent in normal tissues, they provide a high therapeutic index for immunotherapies like the ELI-002 amphiphile vaccine, which targets multiple KRAS mutations (Pant et al., 2024, Nature Medicine). Additionally, adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize specific KRAS peptide-HLA complexes, such as KRAS G12D presented by HLA-C*08:02, have shown clinical efficacy in metastatic disease (Leidner et al., 2022, NEJM). These peptides represent a critical target for overcoming the historical undruggability of KRAS by leveraging the specificity of the adaptive immune system.

Other names

KRAS mutant peptidesKRAS-derived neoepitopesMutant KRAS antigensKRAS-derived tumor-specific antigensmKRAS peptides

Induction of peptide-specific T-cell responses via vaccination or direct targeting of the peptide-HLA complex by engineered T-cell receptors (TCRs) to mediate tumor cell lysis.