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Combination of novel HER2-targeting antibody 1E11 with trastuzumab shows synergistic antitumor activity in HER2-positive gastric cancer.

Author:
  • Bong-Kook Ko
  • Sook-Yeon Lee
  • Young-Ha Lee
  • In-Sik Hwang
  • Helena Persson
  • Johan Rockberg
  • Carl Borrebaeck
  • Dongeun Park
  • Kyu-Tae Kim
  • Mathias Uhlen
  • Jong-Seo Lee
Publishing year: 2015
Language: English
Pages: 398-408
Publication/Series: Molecular Oncology
Volume: 9
Issue: 2
Document type: Journal article
Publisher: Elsevier

Abstract english

The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, improving therapeutic efficacy and patient survival is important, particularly in patients with HER2-positive gastric cancer. Here, we describe the development of 1E11, a HER2-targeted humanized monoclonal antibody showing increased efficacy in a highly synergistic manner in combination with trastuzumab in the HER2-overexpressing gastric cancer cell lines NCI-N87 and OE-19. The two antibodies bind to sub-domain IV of the receptor, but have non-overlapping epitopes, allowing them to simultaneously bind HER2. Treatment with 1E11 alone induced apoptosis in HER2-positive cancer cells, and this effect was enhanced by combination treatment with trastuzumab. Combination treatment with 1E11 and trastuzumab reduced the levels of total HER2 protein and those of aberrant HER2 signaling molecules including phosphorylated HER3 and EGFR. The synergistic antitumor activity of 1E11 in combination with trastuzumab indicates that it could be a novel potent therapeutic antibody for the treatment of HER2-overexpressing gastric cancers.

Keywords

  • Cancer and Oncology

Other

Published
  • CREATE Health
  • ISSN: 1574-7891
Carl B
Carl Borrebaeck
E-mail: carl.borrebaeck [at] immun.lth.se

Professor

Department of Immunotechnology

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Director

Create Health

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