Anti-glypican 3 antibodies cause ADCC against human hepatocellular carcinoma cells

Nakano, Kiyotaka; Orita, Tetsuro; Nezu, Jun-ichi; Yoshino, Takeshi; Ohizumi, Iwao; Sugimoto, Masamichi; Furugaki, Koh; Kinoshita, Yasuko; Ishiguro, Takahiro; Hamakubo, Takao; Kodama, Tatsuhiko; Aburatani, Hiroyuki; Yamada-Okabe, Hisafumi; Tsuchiya, Masayuki

doi:10.1016/j.bbrc.2008.11.033

Cited by 105 publications

(90 citation statements)

References 18 publications

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“…VL regions were cloned into pBluescript KS (+) harboring the constant region of the human kappa chain. The resulting plasmid DNA was transfected into CHO cells by electroporation for further characterization [38].…”

Section: Glypican 3 Targeted Therapy; Antibody-based Approachmentioning

confidence: 99%

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

Allegretta¹,

Filmus²

2011

ACAMC

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Glypican-3 (GPC3) is a developmentally-regulated oncofetal protein that has been established as a clinically-relevant biomarker for early hepatocellular carcinoma (HCC). It is one of the first transcripts to appear during malignant hepatocyte transformation, and is expressed at the protein level in approximately half of high-grade dysplastic macronodules in cirrhotic liver. Several studies show it is expressed in most (75 to 100%) of HCCs confirmed by histopathology. The protein is anchored to the hepatocyte membrane by a glycosyl-phosphatidylinositol (GPI) anchor and shows consistent membrane immunostaining pattern, making it a viable target for immunotherapeutic approaches. Targeting GPC3 for therapeutic intervention is a promising approach for the clinical management of HCC and selected other tumors that express the marker.

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Section: Glypican 3 Targeted Therapy; Antibody-based Approachmentioning

confidence: 99%

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

Allegretta¹,

Filmus²

2011

ACAMC

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show abstract

“…161 Therefore, several anti-GPC3 mAbs have been produced for immunotherapy of HCC, but none of them can inhibit cell proliferation or induce apoptosis. [161][162][163][164] Feng et al 165 identified a human heavy chain variable domain antibody (HN3) targeting GPC3 by phage display technology and proved that HN3 could recognize a unique conformational epitope in the GPC3 core protein with high affinity. The HN3 inhibits cell growth in several hepatoma cell models in vitro and significantly inhibits the growth of HCC tumor-bearing node mice in vivo.…”

mentioning

confidence: 99%

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

Li¹,

Zhang²,

Wang³

et al. 2016

IJN

118

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“…To date, several mouse mAbs against GPC3 have been produced (20)(21)(22)(23)(24)(25)(26)(27), and almost all of them target a peptide derived from GPC3. However, none of these antibodies has shown the ability to inhibit cell proliferation or induce apoptosis, possibly because of the difficulty of having a conventional antibody targeting the potentially cryptic functional epitope of GPC3.…”

mentioning

confidence: 99%

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

Feng

Wang

Chen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

159

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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.heparan sulfate proteoglycans | liver cancer | monoclonal antibodies | phage display | cell growth

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Anti-glypican 3 antibodies cause ADCC against human hepatocellular carcinoma cells

Cited by 105 publications

References 18 publications

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

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

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