Glypican-3 (GPC3) (GPC3)

Glypican-3 (GPC3) is a member of the glypican family of heparan sulfate proteoglycans that are attached to the cell surface via a glycosylphosphatidylinositol (GPI) anchor [UniProt P51654]. It is highly expressed in over 70% of hepatocellular carcinomas (HCC) but is virtually absent in healthy adult tissues, making it an ideal oncofetal antigen for targeted therapy [PMID: 31435174]. GPC3 functions as a co-receptor, modulating several signaling pathways including Wnt, HGF, and IGF, which drive tumor cell proliferation and survival [PMID: 28651541]. Therapeutic approaches targeting GPC3 include monoclonal antibodies like codrituzumab, bispecific T-cell engagers (BiTEs) such as ERY974, and various CAR-T cell therapies [PMID: 33061115]. These agents leverage the high surface density of GPC3 on HCC cells to induce immune-mediated destruction or deliver cytotoxic payloads. Despite its promise, challenges such as the immunosuppressive tumor microenvironment and potential on-target off-tumor effects remain areas of active research [PMID: 35121863].

Other names

GPC3OCI-5MXR7SDYSSGBSGBS1DGSXSecreted glypican-3

Therapeutic agents targeting GPC3 primarily act through immune-mediated mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) for monoclonal antibodies [PMID: 24122134]. Bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cells facilitate direct T-cell lysis of GPC3-expressing cells by forming an immunological synapse [PMID: 29038297, PMID: 33061115]. Additionally, antibody-drug conjugates (ADCs) exploit GPC3-mediated endocytosis to deliver potent cytotoxic payloads directly into the cytoplasm of cancer cells [PMID: 35121863].