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Invest Ophthalmol Vis Sci. 2018 Jun 1;59(7):2687-2698. doi: 10.1167/iovs.18-24024.

Anti-CD160, Alone or in Combination With Bevacizumab, Is a Potent Inhibitor of Ocular Neovascularization in Rabbit and Monkey Models.

Author information

1
Elsalys Biotech, Lyon, France.
2
Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III, Toulouse, France.
3
STROMALab, Université de Toulouse, EFS, ENVT, INSERM U1031, Toulouse, France et LabHPEC, Ecole Nationale Vétérinaire, Toulouse, France.
4
INSERM UMR 976, Hôpital Saint-Louis, Paris, France.
5
Université Paris Diderot-Paris 7, Paris, France.
6
Institut Jean Godinot, Unicancer, F-51726 Reims, France.
7
Université Reims-Champagne-Ardenne, DERM-I-C, EA7319, Reims, France.
8
Mabsolys, Evry, France.
9
Unité de Rétine, Ophthalmology Department, Hôpital Pierre-Paul Riquet, Toulouse University Hospital, Place Baylac, Toulouse, France.
10
Unité Différenciation Epithéliale et Autoimmunité Rhumatoïde UMR 1056 Inserm - Université Toulouse III, Toulouse, France.
11
Université Toulouse III, Toulouse, France.
12
Centre de Recherche en Cancérologie de Toulouse, INSERM UMR1037, Toulouse, France.

Abstract

Purpose:

To assess the efficacy of the murine first-in-class CL1-R2 monoclonal antibody (mAb) targeting human CD160 (alone or in combination with bevacizumab) by using the rabbit corneal neovascularization (CNV) model, and determine the safety and efficacy of ELB01101, a novel CL1-R2-derived humanized IgG4 mAb, in a monkey model of choroidal neovascularization (ChNV).

Methods:

Comparison of effect of CL1-R2, bevacizumab, or aflibercept or IgG1 (control) injections in early and late treatment schemes on evolution of VEGF- or FGF2-induced rabbit CNV was performed. In the combination setting, bevacizumab was coinjected with different doses of CL1-R2. ELB01101 or vehicle was administered intravitreally in monkeys after laser-induced ChNV. Individual laser-induced lesions were semiquantitatively graduated by using fluorescein angiography to determine leakage.

Results:

In the rabbit model, early and late treatments with CL1-R2 significantly decreased both area and length of CNV neovessels. The effect was as potent as produced with anti-VEGF comparators. When combined with bevacizumab, an additive effect of CL1-R2 was measured at all doses tested. In the ChNV model, on day 29, eyes treated with ELB01101 showed a statistically significant reduction in clinically relevant lesions compared to vehicle-treated eyes (∼50%; χ2 test, P = 0.032001).

Conclusions:

The additive effects of anti-CD160 and bevacizumab in the CNV model suggest that these compounds could act via different pathways, opening new therapeutic pathways for cotargeted or combination therapies. In the ChNV model, ELB01101 was well tolerated and prevented approximately 50% of clinically relevant lesions, validating CD160 targeting as a safe approach for treatment of retinal diseases in the most relevant animal model of wet AMD.

PMID:
29860455
DOI:
10.1167/iovs.18-24024
[Indexed for MEDLINE]

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