HN3: a human single-domain monoclonal antibody binds cell surface-associated glypican-3 and inhibits hepatocellular carcinoma cell proliferation

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	CANCER-8

Authors

• M Feng
• W Chen
• D Dimitrov
• M Ho

Abstract

Liver cancer is the fifth most common malignant cancer worldwide. There is an urgent need to develop new drugs with different mechanisms of action. Immunotherapy represents one new approach, but remains a challenge mainly due to lack of tumor-specific targets. Glypican-3 (GPC3) has recently emerged as a promising candidate for liver cancer therapy given that it is highly expressed in HCC. The biological function of GPC3 is largely unknown; nevertheless, it has been suggested to play an important role in cell growth and proliferation via unknown mechanisms. Here, we report a high affinity human single-domain VH monoclonal antibody (named HN3). HN3 binds cell surface-associated GPC3 molecules with sub-nanomolar affinity (KD: 0.2 nM). HN3 recognizes a novel epitope in the core protein of GPC3. The binding of HN3 to GPC3 is independent of the heparan sulfate glycan chains. Furthermore, HN3 can inhibit proliferation of HCC cells and induce apoptosis. Our results show for the first time that it is possible to inhibit HCC cell proliferation by a GPC3 inhibitor. HN3 has potential as a novel therapeutic antibody for liver cancer therapy.

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