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

Biochem Biophys Res Commun. 2009 Jan 9;378(2):279-84. doi: 10.1016/j.bbrc.2008.11.033. Epub 2008 Nov 18.


Glypican 3 (GPC3), a GPI-anchored heparan sulfate proteoglycan, is expressed in the majority of hepatocellular carcinoma (HCC) tissues. Using MRL/lpr mice, we successfully generated a series of anti-GPC3 monoclonal antibodies (mAbs). GPC3 was partially cleaved between Arg358 and Ser359, generating a C-terminal 30-kDa fragment and an N-terminal 40-kDa fragment. All mAbs that induced antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC) against cells expressing GPC3 recognized the 30-kDa fragment, indicating that the C-terminal region of GPC3 serves as an epitope for mAb with ADCC and/or CDC inducing activities. Chimeric mAbs with Fc replaced by human IgG1 were created from GC33, one of the mAbs that reacted with the C-terminal 30-kDa fragment. Chimeric GC33 induced not only ADCC against GPC3-positive human HCC cells but also was efficacious against the Huh-7 human HCC xenograft. Thus, mAbs against the C-terminal 30-kDa fragment such as GC33 are useful in therapy targeting HCC.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity*
  • CHO Cells
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / immunology
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • Glypicans / antagonists & inhibitors*
  • Glypicans / immunology
  • Humans
  • Immunodominant Epitopes / immunology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / immunology
  • Mice
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / immunology
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • GPC3 protein, human
  • Glypicans
  • Immunodominant Epitopes
  • Neoplasm Proteins