Targeting human vasohibin-2 by a neutralizing monoclonal antibody for anti-cancer treatment

Takahiro Koyanagi, Yasuhiro Suzuki, Kazuki Komori, Yasushi Saga, Shigeki Matsubara, Hiroyuki Fujiwara, Yasufumi Sato

研究成果: Article査読

10 被引用数 (Scopus)

抄録

There are two members of the vasohibin (VASH) family, VASH1 and VASH2. VASH1 is expressed mainly in endothelial cells to inhibit angiogenesis, whereas VASH2 is expressed mainly in cancer cells to stimulate tumor growth. The aim of the present study was to establish neutralizing monoclonal antibody (mAb) against human VASH2 and apply it as an anti-cancer treatment. We previously raised mAb against several synthetic peptides of hVASH1, and found that one of them exhibited neutralizing activity against hVASH1. Because of the similarity in the amino acid sequences between VASH1 and VASH2, we hypothesized that they shared the bioactive center. When we mutated four amino acids within the region, the mutant VASH2 lost its pro-angiogenic activity. Therefore, we raised mAb against a synthetic peptide overlapping the mutated amino acids of hVASH2, and isolated one clone (1760) that almost completely inhibited the stimulatory effect of hVASH2 on the migration of and tube formation by endothelial cells. When we used this clone 1760 antibody for cancer treatment, the peritoneal injection of it inhibited both tumor growth and angiogenesis in a mouse xenograft model of human cancer cells. In terms of anti-tumor activity, 25 mg/kg of clone 1760 was equivalent to 5 mg/kg of bevacizmab. From these results, we propose the targeting of human VASH2 with neutralizing mAb as a new strategy for cancer treatment.

本文言語English
ページ(範囲)512-519
ページ数8
ジャーナルCancer science
108
3
DOI
出版ステータスPublished - 2017 3 1

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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