Open AccessTargeting human vasohibin‐2 by a neutralizing monoclonal antibody for anti‐cancer treatment
Author(s) -
Koyanagi Takahiro,
Suzuki Yasuhiro,
Komori Kazuki,
Saga Yasushi,
Matsubara Shigeki,
Fujiwara Hiroyuki,
Sato Yasufumi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13149
Subject(s) - clone (java method) , monoclonal antibody , antibody , microbiology and biotechnology , chemistry , biology , dna , biochemistry , immunology
There are two members of the vasohibin ( VASH ) family, VASH 1 and VASH 2. VASH 1 is expressed mainly in endothelial cells to inhibit angiogenesis, whereas VASH 2 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 VASH 2 and apply it as an anti‐cancer treatment. We previously raised mAb against several synthetic peptides of h VASH 1, and found that one of them exhibited neutralizing activity against h VASH 1. Because of the similarity in the amino acid sequences between VASH 1 and VASH 2, we hypothesized that they shared the bioactive center. When we mutated four amino acids within the region, the mutant VASH 2 lost its pro‐angiogenic activity. Therefore, we raised m A b against a synthetic peptide overlapping the mutated amino acids of h VASH 2, and isolated one clone (1760) that almost completely inhibited the stimulatory effect of h VASH 2 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 VASH 2 with neutralizing m A b as a new strategy for cancer treatment.