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

Summary

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.

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