Purchase this article with an account.
Patrick T Logan, Sultan Aldrees, Mohammed F Qutub, Natalia Vila, Vasco Bravo-Filho, Miguel N Burnier; Evaluating the in vivo efficacy of a novel first in class drug for the treatment of primary uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1291.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The standard for treating uveal melanoma is plaque radiotherapy; however, tumors that are too large or close to the optic nerve cannot be treated using this method. Moreover, as radiotherapy is a non-specific treatment, it can cause serious side-effects, such as retinopathy, cataract, and glaucoma. Thus, there is a need for a specific uveal melanoma treatment with limited side-effects. Herein, we tested the efficacy of a nanoparticle with a conjugated photoactive dye (collectively, AU-011) in a uveal melanoma rabbit model.
One million 92.1 uveal melanoma cells were injected into the suprachoroidal space of twenty albino New Zealand rabbits. Tumor growth was assessed weekly by ultrasound and fundoscopy. After the presence of a tumor was confirmed clinically, treatment commenced. Treatment consisted of intravitreal injection of AU-011; 20 hours after injection, tumors were lasered using an ophthalmic laser (690 nm, 50 J/cm2) to activate the photoactive dye. This treatment was repeated weekly for 3 weeks, and animals were sacrificed 1 week after the last treatment. Post-mortem, tumors were examined on gross pathology and by histopathology.
Twelve of the 20 animals developed intraocular tumors. Two animals with tumors died unexpectedly due to cyclosporine complications and did not receive treatment; these animals acted as controls. For the other 10 treated animals, a noticeable tumor response was observed, which was characterized by three elements: 1) induction of extensive tumor necrosis; 2) change in the growth pattern (“sleeve-like pattern”); and 3) sparing of the adjacent retina. On ultrasound, tumor growth cessation or shrinkage was generally observed. In 4 of these treated animals, histopathology revealed that no tumor was present (complete response); instead, the intraocular masses noted by ultrasound and fundus were comprised of only inflammatory cells and fibrosis. Histopathology of all treated animals showed widespread necrosis (>80% in most cases) that was not seen in controls or in previous animal models (<20% necrosis).
In this pilot study, we show that AU-011 is efficacious for treating uveal melanoma tumors in an orthotopic xenograft rabbit model. In addition to the widespread necrosis noted in treated tumors, several animals experienced complete responses. Future studies investigating different AU-011 dosing regimens are currently underway.
This PDF is available to Subscribers Only