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

The HLA-A*11:01-presented KRAS G12D peptide is a specific neoantigen complex formed by the association of a mutated KRAS peptide fragment with the Human Leukocyte Antigen (HLA) allele A*11:01. KRAS is a member of the RAS family of small GTPases that regulate cell signaling pathways involved in growth and survival; the G12D mutation (substitution of glycine with aspartic acid at position 12) is a frequent driver in several aggressive malignancies, including pancreatic, colorectal, and lung cancers (Sim et al., 2020). In patients possessing the HLA-A*11:01 allele, the intracellular processing of the mutated KRAS protein results in the presentation of the G12D-containing peptide on the cell surface via the MHC Class I pathway. This complex is a highly attractive therapeutic target because it is tumor-specific, absent in normal tissues, and can be recognized by the T-cell receptors (TCRs) of cytotoxic T-lymphocytes (Tran et al., 2016). Current therapeutic approaches targeting this complex include TCR-engineered T-cell (TCR-T) therapies, bispecific T-cell engagers, and personalized cancer vaccines. However, challenges such as HLA loss or downregulation and the requirement for specific patient HLA-typing limit the broader application of these therapies (June et al., 2018).

Other names

KRAS G12D/HLA-A*11:01 complexHLA-A*11:01-restricted KRAS G12D neoantigenKRAS G12D neoepitopepMHC complex HLA-A*11:01:KRAS-G12D

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on cytotoxic T-lymphocytes, leading to targeted lysis of tumor cells.