GTPase KRas G13D mutant neoantigen (KRAS G13D)

The KRAS G13D mutant neoantigen is a tumor-specific protein fragment resulting from a point mutation in the KRAS gene, where glycine at position 13 is substituted by aspartic acid [UniProt: P01116]. This mutation is a frequent driver in various malignancies, particularly colorectal and pancreatic cancers, leading to constitutive activation of downstream signaling pathways like MAPK and PI3K/AKT that promote uncontrolled cell proliferation [PubMed: 30211350]. As a neoantigen, the mutated peptide sequence is processed and presented on the surface of cancer cells by Major Histocompatibility Complex (MHC) molecules, making it a highly specific target for the immune system [PubMed: 26634434]. Therapeutic strategies targeting this neoantigen include cancer vaccines, such as mRNA or peptide-based formulations, and adoptive T-cell therapies using engineered T-cell receptors (TCRs) that recognize the G13D-MHC complex [ClinicalTrials.gov: NCT03948191]. Unlike wild-type KRAS, which is expressed in normal tissues, the G13D neoantigen is unique to tumor cells, potentially offering a wide therapeutic window with minimal off-target toxicity [PubMed: 31549061]. However, challenges remain, including the requirement for specific HLA alleles for presentation and the potential for tumor escape through HLA downregulation [PubMed: 29735921].

Other names

Kirsten rat sarcoma virus oncogene homolog G13DKRAS p.G13DKRAS G13D peptideKRAS G13D neoepitope

Induction of mutation-specific T-cell responses through MHC-restricted recognition of the mutated KRAS G13D peptide sequence [PubMed: 26634434].