Glypican-3-derived peptide-HLA class I complex (GPC3-HLA-I)

The Glypican-3 (GPC3)-derived peptide-HLA class I complex is a tumor-specific antigen target used in the treatment of hepatocellular carcinoma (HCC) and other GPC3-expressing cancers. GPC3 is a heparan sulfate proteoglycan that is significantly overexpressed in HCC but has restricted expression in normal adult tissues, providing a wide therapeutic window (Nakatsura et al., 2003). The target consists of specific GPC3-derived epitopes, such as GPC3(144–152) or GPC3(298–306), presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, typically HLA-A*02:01 or HLA-A*24:02 (Sawada et al., 2012). This complex is recognized by the T-cell receptor (TCR) of CD8+ T cells, making it a focal point for various immunotherapeutic modalities. Current drug development efforts include peptide vaccines, TCR-engineered T-cell (TCR-T) therapies, and TCR-mimic (TCRm) antibodies that can bind the peptide-MHC complex with antibody-like affinity (Liu et al., 2017). These interventions aim to bypass traditional immune checkpoints and directly induce the lysis of malignant cells presenting the GPC3 peptide.

Other names

GPC3 peptide-MHC complexGPC3-HLA-A*02:01 complexGPC3-HLA-A*24:02 complexGlypican-3 peptide-HLA complex

Binding of therapeutic agents (TCRs or TCR-mimic antibodies) to the peptide-HLA complex triggers T-cell mediated cytotoxicity or targeted cell lysis.