Major histocompatibility complex class I presenting epidermal growth factor receptor L858R neoantigen peptide (MHC-I/EGFR-L858R)

The MHC class I presenting EGFR L858R neoantigen peptide is a highly specific therapeutic target primarily relevant in non-small cell lung cancer (NSCLC). The L858R mutation is a common driver mutation in the Epidermal Growth Factor Receptor (EGFR) gene, where leucine is replaced by arginine at position 858. When this mutated protein is processed by the proteasome, it generates unique 'neoantigen' peptides that are not found in healthy cells. These peptides are then loaded onto Major Histocompatibility Complex (MHC) class I molecules, such as HLA-A*02:01, and displayed on the cell surface for surveillance by the immune system. (Source: PubMed, PMID: 30104353; Nature Communications, 2018). This complex serves as a precise 'flag' for the immune system, allowing for the development of targeted immunotherapies like T-cell receptor (TCR)-engineered T-cells and TCR-like antibodies. Unlike traditional EGFR inhibitors that target the protein's kinase activity, therapies targeting the MHC-presented neoantigen aim to selectively destroy cancer cells while sparing healthy tissues that express only wild-type EGFR. This approach is particularly valuable for overcoming resistance to tyrosine kinase inhibitors (TKIs) and providing a more durable immune response. However, the efficacy of targeting this complex depends heavily on the patient's specific HLA type and the consistent expression of MHC molecules by the tumor. (Source: Journal of Hematology & Oncology, 2021; Frontiers in Immunology, 2020).

Other names

HLA-A*02:01/EGFR-L858R complexEGFR L858R neoantigen-MHC complexpMHC complex (EGFR L858R)HLA-restricted EGFR L858R peptide

Targeted cell lysis via T-cell receptor (TCR) recognition of the peptide-MHC complex, leading to the release of perforins and granzymes and subsequent apoptosis of the tumor cell.