Kirsten rat sarcoma viral oncogene homolog G13D mutant peptide antigen (KRAS G13D peptide antigen)

The KRAS G13D mutant peptide antigen is a neoantigen derived from a specific point mutation in the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein, where glycine at position 13 is replaced by aspartic acid. This mutation is a frequent oncogenic driver in various malignancies, particularly colorectal, pancreatic, and lung cancers, leading to constitutive activation of downstream signaling pathways like MAPK/ERK. As a neoantigen, this peptide is processed and presented on the surface of tumor cells by Major Histocompatibility Complex (MHC) molecules, making it a highly specific target for immunotherapy. Therapeutic strategies targeting this antigen include peptide-based vaccines (e.g., ELI-002), mRNA vaccines (e.g., mRNA-5671), and T-cell receptor (TCR) engineered T-cell therapies. These treatments aim to prime the patient's immune system to recognize and eliminate cancer cells harboring the G13D mutation while sparing healthy cells that express the wild-type KRAS protein. However, challenges such as low immunogenicity due to the single amino acid difference and the requirement for specific HLA matching remain significant hurdles in clinical development.

Other names

KRAS G13D neoantigenKRAS G13D mutant epitopeKRAS G13D 25-mer peptideMutant KRAS G13D peptideKRAS G13D tumor-associated antigen

The KRAS G13D mutant peptide antigen acts as a target for immunotherapy by being presented on the surface of tumor cells via Major Histocompatibility Complex (MHC) molecules. Therapeutic vaccines (peptide or mRNA-based) deliver this specific mutant sequence to antigen-presenting cells (APCs), which then prime and activate CD8+ and CD4+ T cells. These activated T cells recognize the KRAS G13D peptide-MHC complex on cancer cells, leading to targeted cell lysis and the induction of a long-term memory immune response against the tumor.