KRAS G12V peptide–HLA-A*02:01–specific T cell receptor (KRAS G12V/HLA-A*02:01 TCR)

The KRAS G12V peptide–HLA-A*02:01–specific T cell receptor is a specialized immune receptor engineered to recognize a specific neoantigen derived from the mutated KRAS protein (Sim et al., 2020). KRAS is a GTPase that regulates cell signaling, and the G12V mutation is a frequent driver in pancreatic, colorectal, and lung cancers (Prior et al., 2020). This TCR specifically binds to the G12V mutant peptide when presented by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule (Bear et al., 2021). In the context of adoptive cell therapy, such as TCR-T, patient T cells are transduced with the gene for this TCR to enable the selective destruction of tumor cells (Wang et al., 2021). Because the G12V mutation is highly tumor-specific and not found in normal tissues, this TCR minimizes the risk of off-target toxicity (June et al., 2018). Clinical candidates like KITE-363 and MDG1015 utilize this or similar TCRs to treat patients with advanced solid tumors (Kite Pharma, 2023; Medigene, 2024). The therapeutic efficacy of this TCR depends on the stable expression of both the mutant protein and the specific HLA allele on the target cell surface (D'Angelo et al., 2018).

Other names

KRAS G12V-specific TCRHLA-A*02:01-restricted KRAS G12V TCRTCR targeting KRAS G12V/HLA-A*02:01KRAS G12V neoantigen-specific T-cell receptor

The TCR-T cells express the specific TCR which binds to the KRAS G12V peptide-HLA-A*02:01 complex on the surface of cancer cells, leading to the formation of an immunological synapse, T-cell activation, and subsequent release of perforins, granzymes, and inflammatory cytokines to induce tumor cell apoptosis.