Mutant RAS neoantigens (RAS neoantigens)

Mutant RAS neoantigens are peptide fragments resulting from somatic mutations in the RAS gene family (primarily KRAS, NRAS, and HRAS) that are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules [Wang et al., 2021, J Hem Onco]. These neoantigens are highly tumor-specific because the underlying mutations, such as the common G12D, G12V, and G12C substitutions, are not present in normal, healthy tissues [Leidner et al., 2022, NEJM]. This specificity makes them ideal targets for various immunotherapeutic modalities, including cancer vaccines, T-cell receptor (TCR) engineered T-cell therapies, and bispecific T-cell engagers [Pant et al., 2024, Nature Medicine]. By targeting these neoepitopes, clinicians aim to trigger a robust and selective cytotoxic T-cell response against RAS-driven malignancies, which are often resistant to conventional therapies [Wang et al., 2021, J Hem Onco]. These targets are particularly relevant in pancreatic, colorectal, and lung cancers where RAS mutations are prevalent drivers of oncogenesis [Leidner et al., 2022, NEJM]. However, the efficacy of these treatments is often restricted by the patient's specific HLA (Human Leukocyte Antigen) type and the potential for tumors to escape immune detection through the loss of HLA expression [Wang et al., 2021, J Hem Onco].

Other names

Mutant KRAS neoantigensMutant NRAS neoantigensMutant HRAS neoantigensRAS-derived neoepitopesMutant RAS-derived peptides

Induction of mutation-specific T-cell responses through the presentation of mutant RAS peptides on MHC molecules, or direct targeting of the peptide-MHC complex by engineered receptors (TCR-T) [Leidner et al., 2022, NEJM; Pant et al., 2024, Nature Medicine].