KRAS G12V peptide-human leukocyte antigen complex (KRAS G12V-HLA complex)

The **KRAS G12V peptide-human leukocyte antigen complex** is a molecular complex formed when a mutant peptide derived from the KRAS protein with a glycine-to-valine mutation at position 12 (G12V) is presented by a class I human leukocyte antigen (most often HLA-A*11:01 or HLA-A*03:01) on the surface of tumor cells[1][2][3][4][6]. This complex acts as a neoantigen, meaning it is present only in tumor cells harboring the mutation and can be specifically recognized by T cell receptors or TCR mimic antibodies engineered for high affinity and specificity[1][2][4][6][9]. This pHLA (peptide-HLA) complex is a promising therapeutic target in cancer immunotherapy, as selective targeting can lead to destruction of KRAS G12V mutant cancer cells without affecting normal tissues[1][2][6]. Its discovery and structural characterization have enabled rational design of adoptive cell therapies and antibody-based modalities, though its use is limited to patients carrying both the mutation and compatible HLA types.

Other names

KRAS G12V neoantigen-HLA complexKRAS G12V mutant peptide-HLA complexmutant KRAS-HLA complexKRAS G12V peptide-MHC class I complex

Recognition and binding of presented mutant KRAS G12V peptide by engineered T cells or TCR-mimic antibodies lead to selective killing of tumor cells expressing the complex[1][2][4][6]. Immune activation via TCR or TCRm engagement with the pHLA (peptide-HLA) surface[2][6]. Initiation of adaptive immune response against tumor cells bearing the KRAS G12V mutation