Kirsten rat sarcoma viral oncogene homolog G12D mutant peptide epitope (KRAS G12D peptide epitope)

The Mutant KRAS G12D peptide epitope is a tumor-specific neoantigen resulting from a point mutation in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, where glycine at position 12 is substituted with aspartic acid (Source: nih.gov [1.1.1]). This mutation is a critical driver in several aggressive cancers, most notably appearing in over 90% of pancreatic ductal adenocarcinomas and approximately 30-50% of colorectal cancers (Source: frontiersin.org [1.2.1]). In the cell, the mutant protein is processed into short peptides that are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, such as HLA-C*08:02 or HLA-A*11:01 (Source: researchgate.net [1.4.1]). These peptide-MHC complexes serve as highly specific targets for the adaptive immune system, as they are absent in normal, healthy tissues (Source: aacrjournals.org [1.3.1]). Therapeutic interventions targeting this epitope include cancer vaccines, such as ELI-002 and Autogene cevumeran, as well as adoptive T-cell therapies (TCR-T) and bispecific T-cell engagers (Source: nih.gov [1.2.2], cancer.gov [1.4.2]). These drugs work by activating or providing T cells that recognize the G12D-MHC complex, leading to the selective lysis of tumor cells (Source: aacrjournals.org [1.4.4]). Clinical challenges include the requirement for specific HLA matching in patients and the potential for tumor escape through the loss of HLA expression (Source: cancer.gov [1.3.2]).

Other names

KRAS G12D neoantigenKRAS G12D neoepitopeMutant KRAS G12D antigenKRAS G12D mutant peptideG12D-mutated KRAS peptide

Induction of antigen-specific T-cell responses or direct T-cell mediated cytotoxicity through recognition of the peptide-MHC complex on the tumor cell surface.