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

Ko, Bong-Kook; Lee, Sook-Yeon; Lee, Young-Ha; Hwang, In-Sik; Persson, Helena LU ; Rockberg, Johan; Borrebaeck, Carl LU ; Park, Dongeun; Kim, Kyu-Tae and Uhlen, Mathias, et al. (2015) In Molecular Oncology 9(2). p.398-408
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
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Molecular Oncology
volume
9
issue
2
pages
398 - 408
publisher
Elsevier
external identifiers
  • pmid:25306393
  • wos:000349582800006
  • scopus:84921371099
ISSN
1574-7891
DOI
10.1016/j.molonc.2014.09.007
project
CREATE Health
language
English
LU publication?
yes
id
b2f8bcac-8bce-4056-9d68-f71195da8f5d (old id 4737104)
date added to LUP
2014-11-10 12:39:38
date last changed
2017-07-30 03:01:37
@article{b2f8bcac-8bce-4056-9d68-f71195da8f5d,
  abstract     = {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.},
  author       = {Ko, Bong-Kook and Lee, Sook-Yeon and Lee, Young-Ha and Hwang, In-Sik and Persson, Helena and Rockberg, Johan and Borrebaeck, Carl and Park, Dongeun and Kim, Kyu-Tae and Uhlen, Mathias and Lee, Jong-Seo},
  issn         = {1574-7891},
  language     = {eng},
  number       = {2},
  pages        = {398--408},
  publisher    = {Elsevier},
  series       = {Molecular Oncology},
  title        = {Combination of novel HER2-targeting antibody 1E11 with trastuzumab shows synergistic antitumor activity in HER2-positive gastric cancer.},
  url          = {http://dx.doi.org/10.1016/j.molonc.2014.09.007},
  volume       = {9},
  year         = {2015},
}