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

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 CRC‐specific molecule, TMEM180, a predicted 11‐pass transmembrane protein that apparently functions as a cation symporter. We developed an anti‐TMEM180 mAb and then succeeded in humanizing the mAb. Immunohistochemistry (IHC) in CRC with the mAb showed a similar positivity rate as compared with anti‐epidermal growth factor receptor mAb, and IHC with anti‐TMEM180 mAb did not show staining in major organs used in this study. Immune electron microscopy clearly indicated that TMEM180 was present on the tumor exosome. The TMEM180 promoter region contains 10 hypoxia‐responsive element consensus sequences; accordingly, SW480 cells upregulated TMEM180 under low‐oxygen conditions. Anti‐TMEM180 mAb has in vitro antibody‐dependent cell‐mediated cytotoxicity and complement‐dependent cytotoxicity 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 therapy against CRC.