Glypican-3-specific T-cell receptor (GPC3-TCR)

The Glypican-3-specific T-cell receptor (GPC3-TCR) is a therapeutic target and molecular tool used in adoptive T-cell therapy to treat GPC3-positive malignancies, most notably hepatocellular carcinoma (HCC). GPC3 is an oncofetal antigen that is highly overexpressed in several solid tumors but has minimal expression in healthy adult tissues, making it an ideal target for immunotherapy. TCRs are engineered to recognize specific GPC3-derived peptides, such as GPC3-144 (FVGEFFTDV) or GPC3-298 (EYILSLEEL), when presented by MHC class I molecules like HLA-A2 or HLA-A24. Upon binding to these peptide-MHC complexes, the TCR initiates a signaling cascade that leads to T-cell activation, proliferation, and the targeted destruction of cancer cells. Clinical development of GPC3-TCR-T therapies aims to overcome the limitations of CAR-T cells in solid tumors by targeting intracellularly processed antigens with high sensitivity.

Other names

T-cell receptor recognizing GPC3-derived peptide–MHC complexesGPC3-specific TCRGlypican-3-targeted T-cell receptorGPC3-pMHC-specific TCR

T-cell receptors (TCRs) engineered to recognize specific Glypican-3 (GPC3) peptides presented by Major Histocompatibility Complex (MHC) molecules (typically HLA-A*02:01 or HLA-A*24:02) allow T cells to specifically identify and eliminate GPC3-expressing tumor cells through the release of cytotoxic granules (perforin/granzymes) and inflammatory cytokines (IFN-gamma, TNF-alpha).