title: Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth.
abstract: Neuropilin-1 (NRP1) guides the development of the nervous and vascular systems. Binding to either semaphorins or VEGF, NRP1 acts with plexins to regulate neuronal guidance, or with VEGFR2 to mediate vascular development. We have generated two monoclonal antibodies that bind to the Sema- and VEGF-binding domains of NRP1, respectively. Both antibodies reduce angiogenesis and vascular remodeling, while having little effect on other VEGFR2-mediated events. Importantly, anti-NRP1 antibodies have an additive effect with anti-VEGF therapy in reducing tumor growth. Vessels from tumors treated with anti-VEGF show a close association with pericytes, while tumors treated with both anti-NRP1 and anti-VEGF lack this organization. We propose that blocking NRP1 function inhibits vascular remodeling, rendering vessels more susceptible to anti-VEGF therapy.
authors.affiliation: Tumor Biology and Angiogenesis, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.forename: Yvan
authors.initials: Y
authors.lastname: Chanthery
authors.forename: Wei-Ching
authors.initials: WC
authors.lastname: Liang
authors.forename: Scott
authors.initials: S
authors.lastname: Stawicki
authors.forename: Judy
authors.initials: J
authors.lastname: Mak
authors.forename: Nisha
authors.initials: N
authors.lastname: Rathore
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Tong
authors.forename: Joe
authors.initials: J
authors.lastname: Kowalski
authors.forename: Sharon Fong
authors.initials: SF
authors.lastname: Yee
authors.forename: Glenn
authors.initials: G
authors.lastname: Pacheco
authors.forename: Sarajane
authors.initials: S
authors.lastname: Ross
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Cheng
authors.forename: Jennifer
authors.initials: J
authors.lastname: Le Couter
authors.forename: Greg
authors.initials: G
authors.lastname: Plowman
authors.forename: Franklin
authors.initials: F
authors.lastname: Peale
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Koch
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Anil
authors.initials: A
authors.lastname: Bagri
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Watts
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009374:Neoplasms, Experimental / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D039942:Neuropilin-1 / Q000276:immunology*; D051381:Rats; D040121:Semaphorin-3A / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D040121:Semaphorin-3A; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1