Kirsten rat sarcoma virus oncogene homolog G12D (KRAS G12D) mutant peptide antigen (KRAS G12D peptide antigen)

The KRAS G12D mutant peptide antigen is a tumor-specific neoantigen derived from the Kirsten rat sarcoma virus oncogene homolog (KRAS) protein carrying a glycine-to-aspartic acid substitution at codon 12. This mutation is a primary driver in several aggressive malignancies, including over 90% of pancreatic ductal adenocarcinomas and significant portions of colorectal and lung cancers. In cancer cells, the mutant protein is processed into short peptide fragments that are presented on the cell surface by specific Human Leukocyte Antigen (HLA) molecules, such as HLA-C*08:02 or HLA-A*11:01. Because this specific peptide sequence is absent in healthy tissues, it serves as an ideal target for precision immunotherapy, including therapeutic vaccines and T-cell receptor (TCR)-engineered T-cell therapies. These treatments aim to stimulate or provide a cytotoxic T-cell response that selectively recognizes and eliminates cells harboring the KRAS G12D mutation. However, challenges such as HLA-restricted eligibility, potential immune evasion through HLA downregulation, and the need for potent adjuvants to overcome weak immunogenicity remain central to the development of therapies targeting this antigen.

Other names

KRAS G12D neoantigenKRAS G12D epitopeMutant KRAS G12D peptideKRAS G12D-derived peptideKRAS G12D-HLA complex

The target is a mutant peptide fragment presented by Human Leukocyte Antigen (HLA) molecules on the surface of cancer cells. Therapeutic agents such as vaccines (e.g., ELI-002) or T-cell receptor (TCR)-engineered T cells (e.g., NT-112) work by inducing or providing T-cell receptors that specifically recognize the peptide-HLA complex. This recognition triggers a cytotoxic immune response, leading to the selective destruction of tumor cells harboring the KRAS G12D mutation while sparing healthy cells that lack the neoantigen.