Kirsten rat sarcoma virus oncogene homolog G12V peptide presented by Human Leukocyte Antigen A*11:01 (KRAS G12V/HLA-A*11:01)

The KRAS G12V peptide presented by HLA-A*11:01 is a tumor-specific neoantigen complex formed when a mutated fragment of the KRAS protein is displayed on the cell surface by the Major Histocompatibility Complex (MHC) class I molecule (Wang et al., 2016, PMID: 27151650). The G12V mutation, involving a substitution of glycine with valine at codon 12, is a frequent driver in several aggressive malignancies, including pancreatic, colorectal, and lung cancers (Prior et al., 2020, PMID: 32103311). This specific peptide-MHC (pMHC) complex is a primary target for precision immunotherapies because it is uniquely present on tumor cells and absent on healthy tissue. Current therapeutic approaches include the development of T-cell receptor (TCR) engineered T-cell therapies, such as AFNT-211, which are designed to recognize and kill cells presenting this specific pMHC (Affini-T Therapeutics, 2024). Additionally, neoantigen vaccines like ELI-002 and mRNA-5671 are being explored to enhance the immune system's ability to detect this complex (NCT04853017; Merck & Co., 2023). Patient selection for these therapies requires dual screening for the KRAS G12V mutation and the HLA-A*11:01 allele. While promising, challenges include potential immune evasion through HLA downregulation and the need to ensure no cross-reactivity with wild-type KRAS peptides (June et al., 2018, PMID: 29973168).

Other names

KRAS G12V-HLA-A*11:01 complexKRAS G12V neoantigenKRAS G12V 7-16 peptide/HLA-A*11:01KRAS G12V:HLA-A*11:01KRAS G12V/HLA-A11

Recognition by engineered T-cell receptors (TCRs) or vaccines to trigger a cytotoxic T-lymphocyte (CTL) response against cells presenting the mutant KRAS peptide.