The characterization of a novel monoclonal antibody against CD93 unveils a new antiangiogenic target.
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Maurizio Orlandini1, Federico Galvagni1, Monia Bardelli1,5, Marina Rocchigiani1, Claudia Lentucci1, Francesca Anselmi1, Alessio Zippo1,6, Luca Bini2, Salvatore Oliviero3,4
1 Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2 – 53100 Siena, Italy.
2 Department of Life Sciences, University of Siena, Via A. Moro, 2 – 53100 Siena, Italy.
3 HuGeF, Via Nizza, 52 – 10126 Torino, Italy.
4 Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina, 13 – 10123 Torino, Italy.
5 Novartis Vaccines, Via Fiorentina, 1 – 53100 Siena, Italy.
6 INGM, Via F. Sforza, 35 – 20122 Milano, Italy.
Maurizio Orlandini, email:
Keywords: monoclonal antibody, endothelial cell, angiogenesis, C1qRp, AA4.
Received: March 12, 2014 Accepted: April 07, 2014 Published: April 07, 2014
The inhibition of tumor angiogenesis is one of the main challenges in cancer therapy. With the aim of developing monoclonal antibodies able to inhibit angiogenesis, we immunized mice with proliferating human umbilical vein endothelial cells. We generated a library of monoclonal antibodies able to recognize antigens expressed on endothelial cells and screened the antibodies for their ability to inhibit endothelial cell proliferation, migration, and sprouting in vitro. Here, we show that the antibody, designated as 4E1, is able to neutralize the formation of new vessels both in vitro and in vivo without affecting endothelial cell survival. By mass spectrometry we identified CD93 as the antigen bound by 4E1 and mapped the recognized epitope. CD93 is a transmembrane protein heavily glycosylated preferentially expressed in the vascular endothelium. CD93 silencing by lentiviral-mediated small hairpin RNA expression impairs human endothelial cell proliferation, migration, and sprouting. Altogether these findings reveal 4E1 as a novel antiangiogenic antibody and identify CD93 as a new target suitable for antiangiogenic therapy.
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