Kirsten rat sarcoma virus oncogene homolog G12D mutant neoantigen (KRAS G12D neoantigen)

KRAS G12D mutant neoantigens are tumor-specific peptides derived from the G12D mutation in the KRAS protein, where a glycine residue is replaced by aspartic acid. These peptides are processed and presented on the surface of cancer cells by Major Histocompatibility Complex (MHC) molecules, making them visible to the immune system as non-self (Leidner et al., 2022, NEJM). Because the G12D mutation is highly prevalent in aggressive cancers such as pancreatic ductal adenocarcinoma and colorectal cancer, these neoantigens are prime targets for immunotherapy (Elicio Therapeutics, 2024). Unlike wild-type KRAS, which is expressed in normal tissues, the G12D neoantigen is unique to the tumor, allowing for high therapeutic specificity and reduced off-target effects. Current therapeutic approaches include cancer vaccines designed to elicit endogenous T-cell responses and adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize the specific KRAS G12D-HLA complex (Moderna, 2023). These strategies aim to overcome the historical difficulty of targeting KRAS directly with small molecules by leveraging the precision of the adaptive immune system.

Other names

KRAS G12D neoepitopeKRAS G12D peptide-HLA complexMutant KRAS G12D antigenKRAS G12D-derived neoantigen

Induction of a mutation-specific T-cell response through the recognition of the KRAS G12D peptide presented on MHC molecules, leading to the selective destruction of mutant-expressing tumor cells.