| Identification of circulating neuropilin-1 and dose-dependent elevation following anti-neuropilin-1 antibody administration. | |
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MedLine Citation:
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PMID: 20068394 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neuropilin-1 (NRP1) acts as a co-receptor for class 3 semaphorins and vascular endothelial growth factor and is an attractive angiogenesis target for cancer therapy. In addition to the transmembrane form, naturally occurring soluble NRP1 proteins containing part of the extracellular domain have been identified in tissues and a cell line. We developed ELISAs to study the existence of circulating NRP1 and to quantify it in serum. As measured by ELISAs, circulating NRP1 levels in mice, rats, monkeys and humans were 427 +/- 77, 20 +/- 3, 288 +/- 86 and 322 +/- 82 ng/ml (mean +/- standard deviation; n > or = 10), respectively. Anti-NRP1(B), a human monoclonal antibody, has been selected from a synthetic phage library. A 4-fold increase in circulating NRP1 was observed in mice receiving a single dose of 10 mg/kg anti-NRP1(B) antibody. In rats and monkeys receiving single injections of anti-NRP1(B) at different dose levels, higher doses of antibody resulted in greater and more prolonged increases in circulating NRP1. Maximum increases were 56- and 7-fold for rats and monkeys receiving 50 mg/kg anti-NRP1(B), respectively. In addition to the soluble NRP1 isoforms, for the first time, a approximately 120 kDa circulating NRP1 protein containing the complete extracellular domain was detected in serum by western blot and mass spectrometry analysis. This protein increased more than the putative soluble NRP1 bands in anti-NRP1(B) treated mouse, rat and monkey sera compared with untreated controls, suggesting that anti-NRP1(B) induced membrane NRP1 shedding. |
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Authors:
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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 |
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Publication Detail:
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Type: Journal Article Date: 2009-07-29 |
Journal Detail:
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Title: mAbs Volume: 1 ISSN: 1942-0870 ISO Abbreviation: MAbs Publication Date: 2009 Jul-Aug |
Date Detail:
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Created Date: 2010-01-13 Completed Date: 2010-04-16 Revised Date: 2010-11-16 |
Medline Journal Info:
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Nlm Unique ID: 101479829 Medline TA: MAbs Country: United States |
Other Details:
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Languages: eng Pagination: 364-9 Citation Subset: IM |
Affiliation:
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Department of Assay and Automation Technology, Genentech Inc., South San Francisco, CA 94080, USA. yanmei@gene.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / administration & dosage, pharmacology* Blotting, Western Cricetinae Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Gene Expression Regulation / drug effects* Humans Mice Neuropilin-1 / blood* Rats |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 144713-63-3/Neuropilin-1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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