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Therapeutically targeting glypican-3 via a novel conformation-specific single-domain antibody in hepatocellular carcinoma

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • Mingq Feng
  • Wei Gao
  • Ruoqi Wang
  • Weiza Chen
  • Yan-G Man
  • Willi Figg
  • Xin W Wang
  • Dimit Dimitrov
  • Mitch Ho


Glypican-3 (GPC3) has emerged as a candidate therapeutic target in hepatocellular carcinoma (HCC), but the oncogenic role of GPC3 in HCC is poorly understood. Here, we report a novel human heavy chain variable domain antibody (HN3) with high affinity (KD = 0.6 nM) for cell surface-associated GPC3 molecules. The human antibody recognized a conformational epitope that requires both the amino and carboxy terminal domains of GPC3. HN3 inhibited proliferation of GPC3-positive cells and exhibited significant HCC xenograft tumor growth inhibition in nude mice. The underlying mechanism of HN3 action may involve cell cycle arrest at G1 phase through yap signaling. This study suggests a novel mechanism for GPC3-targeted cancer therapy.

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