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Yoshitaka Isumi, Tatsuya Inoue, Shinko Hayashi, Chigusa Yoshimura, Jun Hasegawa, Toshiyuki Sato, Toshinori Agatsuma; In vitro characterization of anti-angiogenic effects of DS-7080a, a novel anti-human ROBO4 monoclonal antibody. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1962.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize in vitro the anti-angiogenic effects of DS-7080a, an anti-human roundabout 4 (hROBO4) monoclonal antibody (mAb), possibly indicated for the treatment of angiogenesis-related eye disease such as wet AMD.
DS-7080a antigen-binding activity was measured by a cell enzyme-linked immunosorbent assay. In vitro anti-angiogenic effects contrasting the action of various angiogenic factors were evaluated by a HUVEC migration assay. Primary human retinal pigmented epithelial cells were cultured using Transwell for about one month before collecting conditioned media.
DS-7080a bound to hROBO4 with a Kd of 0.065 nM, while it did not bind to any other ROBO proteins. HUVEC migration was induced by multiple angiogenic factors such as vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor and was inhibited by 37.3, 48.5 and 26.6%, respectively, by 2 μg/mL of DS-7080a. Conditioned media from primary human retinal pigmented epithelial cells was found to induce HUVEC migration, which was inhibited by either DS-7080a (by 77.1% at 1.458 μg/mL) or ranibizumab (by 83.1% at 0.484 μg/mL) alone or in combinaton (125.9%).
DS-7080a shows specific binding to hROBO4 with potent inhibitory effects on HUVEC migration. It may be a therapeutic option for angiogenesis-related diseases where multiple angiogenic factors are involved such as wet AMD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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