KRAS G12D-derived peptide presented by HLA-A*11:01 (KRAS G12D/HLA-A*11:01)

The KRAS G12D-derived peptide presented by HLA-A*11:01 is a tumor-specific neoantigen complex that serves as a primary target for adoptive cell therapies and vaccines. KRAS is a membrane-bound GTPase that regulates signal transduction pathways involved in cell growth; the G12D mutation is a common oncogenic driver, particularly in pancreatic, colorectal, and lung cancers [1][2]. In individuals with the HLA-A*11:01 allele, the mutated KRAS protein is intracellularly processed into specific peptides, such as the 10-mer VVVGADGVGK, which are then displayed on the cell surface by the HLA-A*11:01 molecule [3]. This complex is absent in normal tissues, providing a high degree of tumor specificity for T-cell receptor (TCR) engineered T-cell therapies, such as AFNT-211, which are designed to recognize and eliminate cells expressing this specific neoantigen [4][5]. The interaction between the TCR and the peptide-MHC complex triggers the release of perforins and granzymes, leading to the apoptosis of the cancer cell [6]. However, the effectiveness of targeting this complex can be hindered by tumor-mediated immune evasion mechanisms, such as the loss of HLA expression or the presence of an immunosuppressive tumor microenvironment [7]. Citations: [1] Prior, I. A., et al. (2020) Cancer Discovery; [2] Waters, A. M., & Der, C. J. (2018) Cold Spring Harb Perspect Med; [3] Wang, Q. J., et al. (2016) Cancer Immunol Res; [4] Leidner, R., et al. (2022) NEJM; [5] Affini-T Therapeutics (2023); [6] June, C. H., et al. (2018) Science; [7] Jhunjhunwala, S., et al. (2021) Nat Rev Cancer.

Other names

KRAS G12D neoantigenHLA-A*11:01-restricted KRAS G12D peptideKRAS G12D 7-16 peptidepMHC complex KRAS G12D:HLA-A*11:01KRAS G12D:HLA-A*11:01 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and targeted cytotoxicity.