KRAS proto-oncogene, GTPase G12D peptide-HLA-A*11:01 complex (KRAS G12D/HLA-A*11:01)

The KRAS G12D peptide-HLA-A*11:01 complex is a tumor-specific neoantigen presented on the surface of malignant cells. It consists of a peptide fragment derived from the KRAS protein carrying a glycine-to-aspartic acid mutation at position 12 (G12D), bound to the Major Histocompatibility Complex (MHC) Class I molecule HLA-A*11:01 (Wang et al., 2016). KRAS is a critical GTPase in the MAPK signaling pathway, and the G12D mutation is a primary driver in various aggressive cancers, including pancreatic, colorectal, and lung adenocarcinomas (Simanshu et al., 2017). Because this specific peptide-MHC complex is absent in healthy tissues, it serves as an ideal target for precision immunotherapies such as T-cell receptor (TCR) engineered T-cell therapy and neoantigen vaccines (Affini-T Therapeutics, 2023). Drugs like AFNT-211 are designed to express TCRs that specifically recognize this complex, triggering a targeted cytotoxic immune response against the tumor (Affini-T Therapeutics, 2023). Additionally, vaccines like ELI-002 aim to expand endogenous T-cell populations that can identify this complex to prevent cancer recurrence (Elicio Therapeutics, 2024).

Other names

KRAS G12D neoantigen-MHC complexKRAS G12D-HLA-A*11:01KRAS G12D/A11:01KRAS G12D peptide-MHC complex

Recognition and binding by engineered or endogenous T-cell receptors (TCRs), leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of tumor cells presenting the KRAS G12D neoantigen.