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Feng, Mingqian; Gao, Wei; Wang, Ruoqi; Chen, Weizao; Man, Yan-Gao; Figg, William Douglas; Wang, Xin Wei; Dimitrov, Dimiter S; Ho, Mitchell
Proceedings of the National Academy of Sciences - PNAS, 03/2013, Letnik: 110, Številka: 12Journal Article
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 human heavy-chain variable domain antibody, HN3, with high affinity (K d = 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 inhibition of HCC xenograft tumor growth in nude mice. The underlying mechanism of HN3 action may involve cell-cycle arrest at G1 phase through Yes-associated protein signaling. This study suggests a previously unrecognized mechanism for GPC3-targeted cancer therapy.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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