PlGF blockade does not inhibit angiogenesis during primary tumor growth.
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.
Bais
Carlos
C
Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. bais@gene.com
Wu
Xiumin
X
Yao
Jenny
J
Yang
Suya
S
Crawford
Yongping
Y
McCutcheon
Krista
K
Tan
Christine
C
Kolumam
Ganesh
G
Vernes
Jean-Michel
JM
Eastham-Anderson
Jeffrey
J
Haughney
Peter
P
Kowanetz
Marcin
M
Hagenbeek
Thijs
T
Kasman
Ian
I
Reslan
Hani Bou
HB
Ross
Jed
J
Van Bruggen
Nick
N
Carano
Richard A D
RA
Meng
Yu-Ju Gloria
YJ
Hongo
Jo-Anne
JA
Stephan
Jean-Philippe
JP
Shibuya
Masabumi
M
Ferrara
Napoleone
N
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
D000911:Antibodies, Monoclonal; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D042442:Vascular Endothelial Growth Factors; D000072483:Placenta Growth Factor