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Advances in Liver Cancer Antibody Therapies

A Focus on Glypican-3 and Mesothelin

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Abstract

Liver cancer is one of the most common malignancies worldwide. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the two most common primary liver cancers, yet there have been no significant advances in effective therapeutics. There is an urgent need to identify molecular targets for the development of novel therapeutic approaches. In this review, glypican-3 (GPC3) and mesothelin are discussed, with a focus on their potential as targets for antibody therapy in liver cancer. GPC3 and mesothelin are glycosylphosphatidylinositol-anchored proteins present on the cell surface. They are attractive candidates for liver cancer therapy given that GPC3 and mesothelin show high expression in HCC and CCA, respectively. Antibody drugs targeting GPC3 or mesothelin have shown anti-cancer activity in mice. Humanized or chimeric IgG molecules based on first-generation murine monoclonal antibodies against these antigens are being evaluated in clinical studies. Recently, fully human monoclonal antibodies against GPC3 and mesothelin have been isolated by antibody phage display technology that may provide opportunities for novel cancer therapy.

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Acknowledgments

This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), Center for Cancer Research. Dr Mitchell Ho is also supported by an Ovarian Cancer Research Fund Individual Investigator Award, a Mesothelioma Applied Research Foundation Grant in Honor of Craig Kozicki, a Zi-jiang Lecture Professorship from East China Normal University (Shanghai, China), and the NCI Director’s Intramural Innovation Award for Principal Investigators. Dr Ho is a co-inventor on patents assigned to the US, as represented by the Department of Health and Human Services, for the investigational products. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. The author has no conflict of interest directly relevant to the content of this review.

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  1. Antibody Therapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, 37 Convent Drive, Room 5002C, Bethesda, MD, 20892-4264, USA

    Mitchell Ho

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Ho, M. Advances in Liver Cancer Antibody Therapies. BioDrugs 25, 275–284 (2011). https://doi.org/10.2165/11595360-000000000-00000

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