KRAS G12-mutant peptide presented by HLA-A*11:01 (KRAS G12/HLA-A*11:01)

The KRAS G12-mutant peptide presented by HLA-A*11:01 is a tumor-specific neoantigen complex consisting of a mutated KRAS fragment (typically G12D or G12V) bound to the Human Leukocyte Antigen (HLA) allele A*11:01. KRAS is a membrane-bound GTPase that acts as a molecular switch in the MAPK/ERK signaling pathway; mutations at the G12 position lock the protein in an active state, driving uncontrolled cell proliferation in various cancers, including pancreatic, colorectal, and lung adenocarcinoma (Source: Sim et al., 2021, Cancer Immunology Research). Because these mutations are absent in healthy tissue, the resulting mutant peptides presented on the cell surface by MHC Class I molecules like HLA-A*11:01 serve as highly specific targets for immunotherapy. Therapeutic strategies targeting this complex include adoptive cell transfer using T-cell receptors (TCR-T), bispecific antibodies, and neoantigen vaccines (Source: Affini-T Therapeutics, 2024). These therapies aim to bypass the historically undruggable nature of the KRAS protein by leveraging the immune system's ability to recognize intracellular mutations via surface-presented peptides. Clinical development is particularly focused on patients carrying the HLA-A*11:01 allele, which is prevalent in East Asian populations, making it a key target for precision oncology (Source: Tran et al., 2016, NEJM).

Other names

KRAS G12 mutant peptide-HLA-A*11:01 complexHLA-A*11:01/KRAS G12DHLA-A*11:01/KRAS G12VKRAS G12 neoantigen-MHC complexHLA-A*11:01-restricted KRAS G12 mutant peptide

Recognition of the mutant peptide-HLA complex by engineered or endogenous T-cell receptors (TCRs), triggering cytotoxic T-lymphocyte (CTL) mediated destruction of tumor cells expressing the specific KRAS mutation (Source: Tran et al., 2016, NEJM).