Glypican-3-derived peptide–Human Leukocyte Antigen class I complex (GPC3-HLA-I complex)

The Glypican-3 (GPC3)-derived peptide–Human Leukocyte Antigen (HLA) class I complex is a tumor-specific antigen complex used as a therapeutic target in hepatocellular carcinoma (HCC). GPC3 is an oncofetal protein overexpressed in over 70% of HCC cases but not in healthy adult liver tissue (Nakatsura et al., 2003, Biochem Biophys Res Commun). Intracellular GPC3 is degraded into peptides that are presented on the cell surface by HLA class I molecules, such as HLA-A*02:01 or HLA-A*24:02, where they are recognized by CD8+ T cells (Sawada et al., 2012, Clin Cancer Res). This complex is the focus of various immunotherapeutic strategies, including peptide vaccines, TCR-engineered T-cell (TCR-T) therapies, and TCR-like antibodies (Liu et al., 2017, Gastroenterology). These therapies aim to leverage the high specificity of GPC3 expression to induce a potent anti-tumor immune response while sparing normal tissues. However, challenges such as HLA downregulation by tumor cells and the risk of cytokine release syndrome remain significant considerations in clinical development (Shimizu et al., 2019, Cancer Sci).

Other names

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

The complex acts as a specific target for T-cell receptors (TCRs) or TCR-like antibodies, which triggers the activation of cytotoxic T lymphocytes (CTLs) and leads to the targeted lysis of GPC3-expressing tumor cells.