KRAS G12D peptide–major histocompatibility complex class I complex (KRAS G12D pMHC-I complex)

The KRAS G12D peptide–MHC class I complex is a molecular structure formed when a peptide fragment containing the cancer-associated KRAS G12D mutation (glycine to aspartic acid at position 12) is presented by a major histocompatibility complex class I (MHC-I) molecule, typically alleles such as HLA-A*11:01 or HLA-C*08:02, on the surface of tumor cells. This complex serves as a neoantigen, uniquely marking the tumor cell for immune recognition due to the point mutation in KRAS—a common oncogenic driver in multiple cancer types. T cell receptors (TCRs), whether native or engineered, can specifically bind this pMHC complex, enabling selective targeting and destruction of cancer cells with the KRAS G12D mutation. Immunotherapeutic agents—such as bispecific ImmTAC molecules—have been developed to harness this complex for redirected T cell therapy, demonstrating selectivity and efficacy in preclinical and early clinical investigations. Biomarker selection commonly requires both detection of the KRAS G12D mutation and the presence of a compatible HLA type. Safety issues focus on the potential for cross-reactivity and the fact that therapeutic benefit is restricted to patients harboring both the mutation and the necessary HLA allele.

Other names

KRAS-G12D–HLA class I complexKRAS G12D pHLA complexHLA-A*11:01–KRAS G12D peptide complexHLA-C*08:02–KRAS G12D peptide complex

Antigen-specific T cell redirection and activation Induction of cytotoxic T cell-mediated lysis of KRAS G12D mutant tumor cells Immune mobilization against neoantigen-presenting cancer cells