Kirsten rat sarcoma viral oncogene homolog G12D peptide-Human Leukocyte Antigen-A*11:01 complex (KRAS G12D/HLA-A*11:01)

The Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D peptide-Human Leukocyte Antigen (HLA)-A*11:01 complex is a tumor-specific neoantigen-MHC complex that serves as a critical target for cancer immunotherapy [1, 7]. It consists of a mutated peptide derived from the KRAS protein, specifically harboring the glycine-to-aspartic acid substitution at codon 12 (G12D), presented on the cell surface by the HLA-A*11:01 allele [1, 8]. KRAS G12D is one of the most prevalent driver mutations in human malignancies, particularly in pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer [1, 3]. Because this mutation is absent in normal tissues, the complex represents an ideal "public neoantigen" for precision medicine [4, 5]. Therapeutic strategies targeting this complex include TCR-engineered T cells (TCR-T), bispecific T-cell engagers (such as ImmTACs), and TCR-mimic antibodies, which aim to redirect the immune system to selectively eliminate KRAS-mutant tumor cells [2, 5, 6]. A significant challenge in targeting this complex is the high structural similarity between the mutant and wild-type KRAS peptides, requiring therapeutics with exquisite specificity to avoid off-target effects [4, 8].

Other names

KRAS G12D/HLA-A*11:01KRAS G12D/HLA-A*11KRAS G12D neoantigen-MHC complexKRAS G12D/HLA-A*11:01 pMHCHLA-A*11:01-restricted KRAS G12D complex

T-cell receptor-engineered T-cell therapy (TCR-T) mediated cytotoxicity; Bispecific T-cell engager (TCE) mediated redirection of T-cell cytotoxicity; Antibody-drug conjugate (ADC) mediated delivery of cytotoxic payload