Kirsten rat sarcoma virus oncogene homolog G12V peptide–Human leukocyte antigen A*11:01 complex (KRAS G12V/HLA-A*11:01)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) G12V peptide–Human leukocyte antigen (HLA) A*11:01 complex is a tumor-specific neoantigen presented on the surface of cancer cells. KRAS is a small GTPase that regulates cell signaling; the G12V mutation (glycine to valine at position 12) results in constitutive activation, driving oncogenesis in various solid tumors, including pancreatic, colorectal, and lung cancers [3, 7]. This mutation generates a unique peptide sequence that is processed and presented by the HLA-A*11:01 molecule, a common MHC Class I allele in certain populations [1, 13]. Because this specific peptide-MHC (pMHC) complex is not found on healthy cells, it serves as a highly selective target for immunotherapies such as T-cell receptor-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers [2, 4]. These therapeutic agents are designed to recognize the complex and trigger T-cell-mediated lysis of the tumor cells [11, 12]. Clinical and preclinical studies have identified several TCR clones, such as those used in NW-301V and AFNT-211, which demonstrate potent antitumor activity [2, 7]. However, safety considerations include potential off-target cross-reactivity with similar self-antigens like RAB7B and the management of cytokine release syndrome [1, 5].

Other names

KRAS G12V neoantigenHLA-A*11:01-restricted KRAS G12V epitopeKRAS G12V-HLA-A*11:01 pMHC complexKRAS G12V/HLA-A*11:01

T-cell receptor-engineered T-cell (TCR-T) therapies and T-cell engagers (TCE) are designed to specifically bind the KRAS G12V peptide–HLA-A*11:01 complex, thereby redirecting T-cell cytotoxicity to selectively eliminate tumor cells presenting this neoantigen.