Both the epitope specificity and isotype are important in the antitumor effect of monoclonal antibodies against HER-2/neu antigen

Kwang Mi Kim, Eun Young Shin, Jeoung Hyun Moon, Tae Hwe Heo, Joon Youb Lee, Yeonseok Chung, Yoon Jung Lee, Hyun Mi Cho, Seung Uon Shin, Chang Yuil Kang

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The Her-2/neu oncogene, which encodes a growth factor receptor, was implicated in the malignancy of human adenocarcinomas. Antibodies directed to this molecule have been previously shown to have an antitumor effect in vivo. In an attempt to understand the mechanisms of the antitumor activity, we generated 2 monoclonal antibodies (mAbs), HRO G1 and HRT G1, that recognize different epitopes on Her-2/neu. Both of the mAbs bound HER2/neu on the tumor surface, resulting in phosphorylation of HER2/neu. We also generated IgG2a and IgG2b mAbs from these 2 mAbs, respectively. The results of in vitro studies showed that these anti-Her-2/neu mAbs could not inhibit the growth of the tumor cells that express Her-2/neu molecules by themselves. However, in an antibody-dependent cellular cytotoxicity study using mouse splenocytes as effector cells, HRT mAbs had antitumor activities superior to those of HRO mAbs, indicating that the epitope specificity may also partake in antibody-dependent cellular cytotoxicity with antibody isotype. In a complement-dependent cytotoxicity study, the IgG2a and IgG2b mAbs showed stronger effects than IgG1 isotype mAbs irrespective of the epitope specificities. The results of in vivo studies also showed that HRT mAbs had superior antitumor activity to those of HRO mAbs. The antitumor activity was most prominent in the HRT G2b isotype among HRT mAbs. HRT G1 also showed a moderate antitumor effect, while HRT G2a showed only slight inhibition effect. These data indicate that both the epitope specificity and the differences in Fc region of mAbs could play important roles in the antitumor activities.

Original languageEnglish (US)
Pages (from-to)428-434
Number of pages7
JournalInternational Journal of Cancer
Volume102
Issue number4
DOIs
StatePublished - Dec 1 2002

Keywords

  • Anti-tumor effect
  • Epitope
  • Her-2/neu
  • Isotype
  • Monoclonal antibody

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Kim, K. M., Shin, E. Y., Moon, J. H., Heo, T. H., Lee, J. Y., Chung, Y., Lee, Y. J., Cho, H. M., Shin, S. U., & Kang, C. Y. (2002). Both the epitope specificity and isotype are important in the antitumor effect of monoclonal antibodies against HER-2/neu antigen. International Journal of Cancer, 102(4), 428-434. https://doi.org/10.1002/ijc.10732