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Cet abstract a été assigné à session OB Free papers 3 - Medical retina
TitreEfficacy of Placental growth factor Inhibition in AMD
ButWe previously showed that an anti-PlGF antibody (5D11D4) inhibits choroidal neovascularization (CNV) in a mouse model of AMD. An additive effect was shown in combination therapy with an anti-VEGFR antibody. Specificity of 5D11D4 was assessed in this study.
MéthodesCNV was induced in mice by placing 3 laser burns on the choroid. Mice with a genetic loss of PlGF; a lacking tyrosin kinase domain of the Flt-1R or a knock-down of the monocyte chemoattractive protein were generated. The optimal dose of 25mg/kg of 5D11D4 was injected in all mice ip. 3 times a week.
RésultatsIn a first experiment loss of PlGF inhibited CNV. However, administration of 5D11D4 to PlGF-/- mice did not inhibit CNV further than in control-treated PlGF-/- mice. Second, CNV lesions in Ccl2-/- mice were slightly larger than in WT mice within 14 days after laser-injury. Notably, 5D11D4 was able to inhibit CNV again by 53%. Third, CNV lesions were reduced by 70% in Flt1-TK-/- mice, comparably as observed in PlGF-/- mice. 5D11D4 was unable to inhibit CNV in Flt1-TK-/- mice any further, suggesting that PlGF works specifically via Flt1. Fourth, we also tested the murine anti-human PlGF mAb 16D3 in humanized PlGF-/- mice. Human PlGF-2 increased laser-induced CNV after 5 days, but this increase was again blocked by 16D3. And finally, of two other anti-mPlGF mAbs, 3C7A8 and 12H6B6, the first one inhibited CNV, while 12H6B6 was ineffective, showing that anti-PlGF mAb clones with proven efficacy in vitro are not necessarily effective in blocking PlGF-driven processes in vivo.
ConclusionWe have proven that 5D11D4 specifically inhibits laser-induced CNV formation, in different transgenic models and that this effect is mediated via the Flt1 receptor.
Auteur 1
NomVAN DE VEIRE
InitialesS
InstitutUZL
VilleLeuven
Auteur 2
NomVan Bergen
InitialesT
InstitutKUL
VilleLeuven
Auteur 3
NomMoons
InitialesL
InstitutKUL
VilleLeuven
Auteur 4
NomCarmeliet
InitialesP
InstitutKUL
VilleLeuven
Auteur 5
NomStalmans
InitialesI
InstitutUZL
VilleLeuven
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