Glypican-1-Targeted Antibody-Drug Conjugate Exhibits Antitumor Effects Against Oral Squamous Cell Carcinoma.

Abstract

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 (IC5₅₀ = 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.