Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5505852 | Biochemical and Biophysical Research Communications | 2017 | 6 Pages |
Abstract
EGFR-mutant lung adenocarcinomas contain a subpopulation of cells that have undergone epithelial-to-mesenchymal transition and can grow independently of EGFR. To kill these cancer cells, we need a novel therapeutic approach other than EGFR inhibitors. If a molecule is specifically expressed on the cell surface of such EGFR-independent EGFR-mutant cancer cells, it can be a therapeutic target. We found that a mesenchymal EGFR-independent subline derived from HCC827Â cells, an EGFR-mutant lung adenocarcinoma cell line, expressed angiotensin-converting enzyme 2 (ACE2) to a greater extent than its parental cells. ACE2 was also expressed at least partially in most of the primary EGFR-mutant lung adenocarcinomas examined, and the ACE2 expression level in the cancer cells was much higher than that in normal lung epithelial cells. In addition, we developed an anti-ACE2 mouse monoclonal antibody (mAb), termed H8R64, that was internalized by ACE2-expressing cells. If an antibody-drug conjugate consisting of a humanized mAb based on H8R64 and a potent anticancer drug were produced, it could be effective for the treatment of EGFR-mutant lung adenocarcinomas.
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Authors
Miki Yamaguchi, Sachie Hirai, Toshiyuki Sumi, Yusuke Tanaka, Makoto Tada, Yukari Nishii, Tadashi Hasegawa, Hiroaki Uchida, Gen Yamada, Atsushi Watanabe, Hiroki Takahashi, Yuji MD, PhD,