Identification of circulating neuropilin-1 and dose-dependent elevation following anti-neuropilin-1 antibody administration

• DOI: 10.4161/mabs.1.4.8885
• Publication Date: 2010-07-01T18:04:20Z
• Authors: Yanmei Lu; Hong Xiang; Peter Liu; Raymond R. Tong; Ryan J. Watts; Alexander W. Koch; Wendy N. Sandoval; Lisa A. Damico; Wai Lee Wong; Y. Gloria Meng
• Keywords: Neuropilin

Neuropilin-1 (NRP1) acts as a co-receptor for class 3 semaphorins and vascular endothelial growth factor is an attractive angiogenesis target cancer therapy. In addition to the transmembrane form, naturally occurring soluble NRP1 proteins containing part of extracellular domain have been identified in tissues cell line. We developed ELISAs study existence circulating quantify it serum. As measured by ELISAs, levels mice, rats, monkeys humans were 427 ± 77, 20 3, 288 86 322 82 ng/ml (mean standard deviation; n ≥ 10), respectively. Anti-NRP1B, human monoclonal antibody, has selected from synthetic phage library. A 4-fold increase was observed mice receiving single dose 10 mg/kg anti-NRP1B antibody. rats injections at different levels, higher doses antibody resulted greater more prolonged increases NRP1. Maximum 56- 7-fold 50 anti-NRP1B, isoforms, first time, ~120 kDa protein complete detected serum Western blot mass spectrometry analysis. This increased than putative bands treated mouse, rat monkey sera compared with untreated controls, suggesting that induced membrane shedding.