Glypican‐1‐Targeted Antibody–Drug Conjugate Exhibits Antitumor Effects Against Oral Squamous Cell Carcinoma

Background Oral squamous cell carcinoma (OSCC) is a major health concern with limited therapeutic options. Glypican‐1 (GPC1), a heparan sulphate proteoglycan, has been implicated in several malignancies; however, its therapeutic role in OSCC remains elusive. This study investigated the potential of a novel glypican‐1 antibody–drug conjugate (GPC1‐ADC) conjugated with monomethyl auristatin E as a therapeutic strategy for OSCC. Methods GPC1 expression in OSCC tissues was examined by immunohistochemistry using tissue microarrays and by western blotting in OSCC cell lines. The cytotoxicity of GPC1‐ADC was assessed using in vitro viability assays, and its effects on the cell cycle and apoptosis were analyzed using flow cytometry and caspase‐3/7 activity assays. In vivo antitumor efficacy was evaluated using OSCC cell line–derived and patient‐derived xenograft (PDX) mouse models. Results High GPC1 expression was observed in 78% (39/50) of OSCC cases, whereas normal oral tissues showed no detectable expression. Western blotting confirmed GPC1 protein expression in all the OSCC cell lines tested. GPC1‐ADC markedly reduced cell viability in a dose‐dependent manner (IC5 50 = 0.053–0.117 nM), induced G2/M‐phase arrest, and activated caspase‐3/7, indicating apoptosis. In vivo, high‐dose GPC1‐ADC markedly inhibited tumor growth in both xenograft and PDX models compared with control treatments, without causing weight loss. Conclusion GPC1‐ADC demonstrated potent and specific antitumor activity against GPC1‐expressing OSCC in vitro and in vivo. These findings suggest that GPC1‐ADC is a promising therapeutic candidate for OSCC and may provide a basis for new treatment strategies; however, further preclinical and clinical evaluation is warranted.