Mutant KRAS and NRAS neoantigenic peptides presented by Major Histocompatibility Complex (Mutant RAS-MHC complex)

Mutant KRAS and NRAS neoantigenic peptides presented by the Major Histocompatibility Complex (MHC) are specific protein fragments derived from mutated RAS proteins displayed on the surface of tumor cells. KRAS and NRAS are essential GTPases that regulate intracellular signaling pathways controlling cell proliferation and survival (Simanshu et al., 2017). Mutations at specific hotspots, such as G12, G13, or Q61, lead to constitutive activation and are primary drivers in pancreatic, colorectal, and lung cancers (Prior et al., 2020). These mutations create unique amino acid sequences, known as neoantigens, which are processed and presented by MHC molecules to the immune system. This presentation enables the development of highly specific immunotherapies, including TCR-engineered T cells and neoantigen vaccines, which target tumor cells while sparing healthy tissue (Bear et al., 2022). Therapeutic strategies like ELI-002 and mRNA-5671 aim to prime the immune system to recognize these specific peptide-MHC complexes (Elicio Therapeutics, 2024). While these targets are highly specific, their application is restricted by the diversity of human leukocyte antigen (HLA) types, requiring treatments to be matched to a patient's specific HLA profile. Additionally, tumors may escape detection by downregulating MHC expression or through other mechanisms of immune evasion (Leidner et al., 2022).

Other names

Mutant KRAS/NRAS neoepitopesRAS-derived neoantigensMutant RAS-HLA complexKRAS/NRAS pMHCMutant RAS peptides presented by MHC

Recognition of specific mutant RAS peptide-MHC complexes by T-cell receptors (TCRs) or TCR-mimic agents to induce targeted cytotoxic T-lymphocyte activation and tumor cell lysis.