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Int J Cancer. 2018 Mar 1;142(5):1056-1066. doi: 10.1002/ijc.31124. Epub 2017 Oct 31.

Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer.

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Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Yamadaoka Suita, Osaka, Japan.
Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Center for Intractable Immune Disease, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
Department of Pathology, Osaka University Graduate School of Medicine, Yamadaoka Suita, Osaka, Japan.


Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression. The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was potently cytotoxic to cancer cells highly expressing GPC1. There were no inhibitory effects on cancer cells with low expression of GPC1. In a murine xenograft model, GPC1-ADC also had significant and potent tumor growth inhibition. GPC1-ADC-mediated G2/M phase cell cycle arrest was detected, indicating that the dominant antitumor effect in vivo was MMAF-mediated. The toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our data showed that GPC1-ADC has potential as a promising therapy for uterine cervical cancer.


antibody-drug conjugate; glypican-1; uterine cervical cancer

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