Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer-specific molecule.

Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer-specific molecule.

Cancer Sci. 2018 Dec 08;:

Authors: Yasunaga M, Saijou S, Hanaoka S, Anzai T, Tsumura R, Matsumura Y

Abstract
The present state of therapy for colorectal cancer (CRC) is far from satisfactory, highlighting the need for new targets for this disease. We identified a new colorectal cancer (CRC)-specific molecule, TMEM180, a predicted eleven-pass transmembrane protein that apparently functions as a cation symporter. We developed the anti-TMEM180 monoclonal antibody (mAb) and then succeeded in humanizing the mAb. Immunohistochemistry (IHC) in CRC with the mAb showed a similar positivity rate as compared with anti-EGFR mAb and the IHC with anti-TMEM180 mAb did not show staining in major organs used in this study. The immune-electron microscopy clearly indicated that TMEM180 was present on the tumor exosome. The TMEM180 promoter region contains ten hypoxia-responsive element consensus sequences; accordingly SW480 cells upregulated TMEM180 under low-oxygen conditions. The anti-TMEM180 mAb possessed in vitro ADCC and CDC activity, and SW480 CRC xenografts were eradicated by the mAb. These data indicate that TMEM180 may be a new CRC marker and that a mAb against this protein could be used as antibody-based therapeutic against CRC. This article is protected by copyright. All rights reserved.

PMID: 30537002 [PubMed - as supplied by publisher]

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