title: PlGF blockade does not inhibit angiogenesis during primary tumor growth.
abstract: It has been recently reported that treatment with an anti-placenta growth factor (PlGF) antibody inhibits metastasis and primary tumor growth. Here we show that, although anti-PlGF treatment inhibited wound healing, extravasation of B16F10 cells, and growth of a tumor engineered to overexpress the PlGF receptor (VEGFR-1), neutralization of PlGF using four novel blocking antibodies had no significant effect on tumor angiogenesis in 15 models. Also, genetic ablation of the tyrosine kinase domain of VEGFR-1 in the host did not result in growth inhibition of the anti-VEGF-A sensitive or resistant tumors tested. Furthermore, combination of anti-PlGF with anti-VEGF-A antibodies did not result in greater antitumor efficacy than anti-VEGF-A monotherapy. In conclusion, our data argue against an important role of PlGF during primary tumor growth in most models and suggest that clinical evaluation of anti-PlGF antibodies may be challenging.
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. bais@gene.com
authors.forename: Carlos
authors.initials: C
authors.lastname: Bais
authors.forename: Xiumin
authors.initials: X
authors.lastname: Wu
authors.forename: Jenny
authors.initials: J
authors.lastname: Yao
authors.forename: Suya
authors.initials: S
authors.lastname: Yang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Crawford
authors.forename: Krista
authors.initials: K
authors.lastname: McCutcheon
authors.forename: Christine
authors.initials: C
authors.lastname: Tan
authors.forename: Ganesh
authors.initials: G
authors.lastname: Kolumam
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vernes
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Eastham-Anderson
authors.forename: Peter
authors.initials: P
authors.lastname: Haughney
authors.forename: Marcin
authors.initials: M
authors.lastname: Kowanetz
authors.forename: Thijs
authors.initials: T
authors.lastname: Hagenbeek
authors.forename: Ian
authors.initials: I
authors.lastname: Kasman
authors.forename: Hani Bou
authors.initials: HB
authors.lastname: Reslan
authors.forename: Jed
authors.initials: J
authors.lastname: Ross
authors.forename: Nick
authors.initials: N
authors.lastname: Van Bruggen
authors.forename: Richard A D
authors.initials: RA
authors.lastname: Carano
authors.forename: Yu-Ju Gloria
authors.initials: YJ
authors.lastname: Meng
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: Hongo
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Stephan
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
authors.forename: Napoleone
authors.initials: N
authors.lastname: Ferrara
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors
chemical_list: D000911:Antibodies, Monoclonal; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D042442:Vascular Endothelial Growth Factors; D000072483:Placenta Growth Factor