Targeting multiple Her-2 epitopes with monoclonal antibodies results in improved antigrowth activity of a human breast cancer cell line in vitro and in vivo

Camelia I. Spiridon, Maria Ana Ghetie, Jonathan Uhr, Radu Marches, Jia Ling Li, Guo Liang Shen, Ellen S. Vitetta

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Her-2 (p185erbB-2) is a transmembrane tyrosine kinase receptor, which is encoded by the Her-2/neu proto-oncogene. Her-2 is overexpressed on 30% of highly malignant breast cancers. Monoclonal antibodies (MAbs) against Her-2 inhibit the growth of Her-2-overexpressing tumor cells and this occurs by a variety of mechanisms. One such MAb, Herceptin (Trastuzumab), has been approved for human use. We have generated a panel of murine anti-Her-2 MAbs against nine different epitopes on the extracellular domain of Her-2 and have evaluated the antitumor activity of three of these MAbs alone and in combination, both in vitro and in vivo. We found that MAbs (against different epitopes) make a highly effective mixture, which was more effective than the individual MAbs in treating s.c. tumor nodules of BT474 cells in SCID mice. In vitro, the MAb mixture was also more effective than the single MAbs in inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, inhibiting cell growth and inducing apoptosis, and inhibiting the secretion of vascular endothelial growth factor. Taken together, these activities might explain the superior performance of the MAb mixture in vivo.

Original languageEnglish (US)
Pages (from-to)1720-1730
Number of pages11
JournalClinical Cancer Research
Volume8
Issue number6
StatePublished - 2002

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Human Activities
Epitopes
Monoclonal Antibodies
Breast Neoplasms
Cell Line
SCID Mice
Proto-Oncogenes
Receptor Protein-Tyrosine Kinases
Growth
Vascular Endothelial Growth Factor A
In Vitro Techniques
Neoplasms
Apoptosis
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Targeting multiple Her-2 epitopes with monoclonal antibodies results in improved antigrowth activity of a human breast cancer cell line in vitro and in vivo. / Spiridon, Camelia I.; Ghetie, Maria Ana; Uhr, Jonathan; Marches, Radu; Li, Jia Ling; Shen, Guo Liang; Vitetta, Ellen S.

In: Clinical Cancer Research, Vol. 8, No. 6, 2002, p. 1720-1730.

Research output: Contribution to journalArticle

Spiridon, Camelia I. ; Ghetie, Maria Ana ; Uhr, Jonathan ; Marches, Radu ; Li, Jia Ling ; Shen, Guo Liang ; Vitetta, Ellen S. / Targeting multiple Her-2 epitopes with monoclonal antibodies results in improved antigrowth activity of a human breast cancer cell line in vitro and in vivo. In: Clinical Cancer Research. 2002 ; Vol. 8, No. 6. pp. 1720-1730.
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AU - Marches, Radu

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AU - Shen, Guo Liang

AU - Vitetta, Ellen S.

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