Human monoclonal antibodies specific for glypican-3 and use thereof

Abstract

Described herein is the identification of human monoclonal antibodies that bind GPC3 or heparan sulfate (HS) chains on GPC3 with high affinity. The antibodies described herein are capable of inhibiting HCC cell growth and migration. Provided are human monoclonal antibodies specific for GPC3 or HS chains on GPC3, including immunoglobulin molecules, such as IgG antibodies, as well as antibody fragments, such as single-domain VH antibodies or single chain variable fragments (scFv). Further provided are compositions including the antibodies that bind GPC3 or HS chains on GPC3, nucleic acid molecules encoding these antibodies, expression vectors comprising the nucleic acids, and isolated host cells that express the nucleic acids. Methods of treating cancer and / or inhibiting tumor growth or metastasis are also provided. Further provided are methods of detecting cancer in a subject and confirming a diagnosis of cancer in a subject.

Description

[0001] Cross References to Related Applications

[0002] This application claims the benefit of US Provisional Application No. 61 / 477,020, filed April 19, 2011, which is incorporated herein by reference in its entirety. technical field

[0003] The present disclosure relates to antibodies specific for Glypican 3 (GPC3) or heparan sulfate on GPC3 and their use for the treatment of cancer. Background technique

[0004] Liver cancer is the fifth most prevalent tumor and the third most common cause of cancer-related death in the world (Bosch et al., Gastroenterology 127:S5-S16, 2004; El-Serag et al., Gastroenterology 132: 2557-76, 2007). According to the American Cancer Society, hepatocellular carcinoma (HCC) accounts for approximately 75 percent of liver cancer cases. Symptoms often do not appear until advanced liver cancer. Surgery is the standard treatment for liver cancer because this type of cancer does not respond well to most chemotherapy drugs. Therefore, there is an...

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