KRAS G12V mutant peptide-HLA class I complex (KRAS G12V/HLA-I)

The KRAS G12V mutant peptide presented by HLA class I is a tumor-specific neoantigen complex that serves as a high-priority target for cancer immunotherapy. KRAS is a member of the RAS GTPase family that acts as a molecular switch for signaling pathways involved in cell growth; the G12V mutation results in a constitutively active protein that drives oncogenesis in pancreatic, colorectal, and lung cancers (Simanshu et al., 2017). Because the G12V mutation is somatic and tumor-specific, the resulting mutant peptide is not found in normal tissues, making the peptide-HLA (pHLA) complex an ideal target for avoiding off-target toxicity. Therapeutic approaches targeting this complex include T-cell receptor (TCR) engineered T-cells (TCR-T) and neoantigen vaccines, which aim to activate cytotoxic T-lymphocytes to recognize and eliminate tumor cells (Leidner et al., 2022). The effectiveness of these therapies is dependent on the patient's specific HLA genotype, as only certain HLA alleles, such as HLA-A*11:01, can effectively present the G12V peptide to the immune system (Wang et al., 2016). Current clinical development focuses on identifying high-affinity TCRs and multi-valent vaccines to overcome challenges such as HLA downregulation and tumor heterogeneity (Bear et al., 2021).

Other names

KRAS G12V neoantigenKRAS G12V-MHC complexKRAS G12V-HLA-A*11:01 complexKRAS G12V-HLA-A*03:01 complexKRAS G12V-HLA-A*02:01 complex

T-cell receptor (TCR) mediated recognition of the peptide-HLA complex leading to T-cell activation and tumor cell lysis (Leidner et al., 2022).