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

Masahiro Yasunaga1, Shinji Saijou1, Shingo Hanaoka1

  • 1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Centre, National Cancer Centre, Kashiwa, Japan.

Cancer Science
|December 12, 2018
PubMed

Insights

Researchers discovered TMEM180, a novel colorectal cancer (CRC) target. An antibody targeting TMEM180 shows promise for CRC diagnosis and antibody-based therapy, eradicating tumors in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Current colorectal cancer (CRC) therapies are insufficient, necessitating novel therapeutic targets.
  • TMEM180, an 11-pass transmembrane protein functioning as a cation symporter, has been identified as a CRC-specific molecule.

Purpose of the Study:

  • To investigate TMEM180 as a potential diagnostic marker and therapeutic target for colorectal cancer.
  • To develop and characterize an anti-TMEM180 monoclonal antibody (mAb) for CRC treatment.

Main Methods:

  • Development and humanization of an anti-TMEM180 mAb.
  • Immunohistochemistry (IHC) to assess TMEM180 expression in CRC tissues and normal organs.
  • Immune electron microscopy to localize TMEM180 on tumor exosomes.
  • Assessment of TMEM180 upregulation under hypoxic conditions.
  • Evaluation of in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
  • In vivo efficacy study using SW480 CRC xenografts.

Main Results:

  • TMEM180 is specifically expressed in CRC with minimal staining in major organs.
  • TMEM180 is localized on tumor exosomes and its expression is upregulated under hypoxia.
  • The anti-TMEM180 mAb demonstrated significant in vitro cytotoxic activity (ADCC and CDC).
  • SW480 CRC xenografts were eradicated by the anti-TMEM180 mAb treatment.

Conclusions:

  • TMEM180 represents a promising new biomarker for colorectal cancer.
  • An antibody targeting TMEM180 holds potential for novel antibody-based CRC therapy.
Keywords:
antibody drugantibody therapydiagnosis by tumor marker and biomarkergastrointestinal tracttumor antigen

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