IL-18 Immunotherapy for Neovascular AMD: Tolerability and Efficacy in Nonhuman Primates.
Invest Ophthalmol Vis Sci
; 56(9): 5424-30, 2015 Aug.
Article
in En
| MEDLINE
| ID: mdl-26284546
ABSTRACT
PURPOSE:
Age-related macular degeneration is the most common form of central retinal blindness in the elderly. Of the two end stages of disease, neovascular AMD-although the minority form-is the most severe. Current therapies are highly successful at controlling progression of neovascular lesions; however, a significant number of patients remain refractory to treatment and the development of alternative and additive therapies to anti-VEGFs is essential.METHODS:
In order to address the translational potential of interleukin (IL)-18 for use in neovascular AMD, we initiated a nonhuman primate tolerability and efficacy study for the use of intravitreally (IVT) administered clinical grade human IL-18 (SB-485232). Cynomolgus monkeys were injected IVT with increasing doses of human IL-18 (two each at 1000, 3000, and 10,000 ng per eye). In tandem, 21 monkeys were administered nine laser burns in each eye prior to receiving IL-18 as an IVT injection at a range of doses. Fundus fluorescein angiography (FFA) was performed on days 8, 15, and 22 post injection and the development of neovascular lesions was assessed.RESULTS:
We show intravitreal, mature, recombinant human IL-18 is safe and can reduce choroidal neovascular lesion development in cynomolgus monkeys.CONCLUSIONS:
Based on our data comparing human IL-18 to current anti-VEGF-based therapy, clinical deployment of IL-18 for neovascular AMD has the potential to lead to a new adjuvant immunotherapy-based treatment for this severe form of central blindness.
Full text:
1
Database:
MEDLINE
Main subject:
Retinal Neovascularization
/
Interleukin-18
/
Endothelial Cells
/
Immunotherapy
/
Macular Degeneration
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Year:
2015
Type:
Article