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 Citations (Scopus)

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

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Epitopes
Monoclonal Antibodies
Antigens
Antibodies
Neoplasms
Growth Factor Receptors
Oncogenes
Adenocarcinoma
Immunoglobulin G
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Both the epitope specificity and isotype are important in the antitumor effect of monoclonal antibodies against HER-2/neu antigen. / Kim, Kwang Mi; Shin, Eun Young; Moon, Jeoung Hyun; Heo, Tae Hwe; Lee, Joon Youb; Chung, Yeonseok; Lee, Yoon Jung; Cho, Hyun Mi; Shin, Seung-Uon; Kang, Chang Yuil.

In: International Journal of Cancer, Vol. 102, No. 4, 01.12.2002, p. 428-434.

Research output: Contribution to journalArticle

Kim, Kwang Mi ; Shin, Eun Young ; Moon, Jeoung Hyun ; Heo, Tae Hwe ; Lee, Joon Youb ; Chung, Yeonseok ; Lee, Yoon Jung ; Cho, Hyun Mi ; Shin, Seung-Uon ; Kang, Chang Yuil. / Both the epitope specificity and isotype are important in the antitumor effect of monoclonal antibodies against HER-2/neu antigen. In: International Journal of Cancer. 2002 ; Vol. 102, No. 4. pp. 428-434.
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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.",
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AU - Kim, Kwang Mi

AU - Shin, Eun Young

AU - Moon, Jeoung Hyun

AU - Heo, Tae Hwe

AU - Lee, Joon Youb

AU - Chung, Yeonseok

AU - Lee, Yoon Jung

AU - Cho, Hyun Mi

AU - Shin, Seung-Uon

AU - Kang, Chang Yuil

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Y1 - 2002/12/1

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AB - 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.

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KW - Epitope

KW - Her-2/neu

KW - Isotype

KW - Monoclonal antibody

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