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Patrick T Logan, Pablo Zoroquiain, Sultan Aldrees, Mohammed F. Qutub, Natalia Vila, Miguel N Burnier; Assessment of the activity of different AU-011 doses in a xenograft uveal melanoma model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4111.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma is an intraocular tumor that lacks tumor-specific treatment. We previously demonstrated the efficacy of a first-in-class tumor-targeting therapy, which utilizes a viral-like nanoparticle derived from a virus capsid conjugated to a photoactive dye (collectively AU-011), in a rabbit model of uveal melanoma. Herein, we evaluated the efficacy of 3 different AU-011 doses.
The xenograft uveal melanoma animal model using human cells was generated as previously described. Once tumors were identified via ultrasound and fundus examination, treatment commenced. Animals were randomly divided into four groups: 1, vehicle control; 2, once weekly treatment of 50µg for 6 consecutive weeks; 3, twice weekly treatment of 20µg for 3 consecutive weeks; and 4, twice weekly treatment of 5µg AU-011 doses for 3 consecutive weeks. All treatments, save vehicle, consisted of an intravitreal injection of AU-011, followed by lasering the tumor using an ophthalmic laser (690nm, 50 J/cm2) to activate the photoactive dye 6±1 hours after injection. Vehicle animals received saline and no laser. Animals were sacrificed 1 week after the final treatment, and tumors were evaluated by gross and histopathology.
Ten animals developed treatable tumors; 2 animals in group 1, 3 in group 2, 2 in group 3, and 3 in group 4. All animals that received AU-011 + laser exhibited a marked response, manifested as extensive tumor necrosis. Three animals experienced complete tumor response (1 in group 3, 2 in group 4); these animals had significantly smaller mean tumor size upon treatment commencement (2.2 disc diameter [DD] ± 0.2 vs 4.3 ± 1.7 DD for all other treated rabbits; P = 0.029). Tumors in group 2 were >80% necrotic, while the control tumors had mean necrosis of <40%. Animals with twice weekly treatments (groups 3 and 4) showed intraocular inflammation that is assumed to have been generated by acute tumor necrosis over a short period of time. Inflammation was not observed in the once weekly administration group.
AU-011 shows consistent efficacy mediated by tumor necrosis in uveal melanoma tumors in a rabbit xenograft model. Two treatment doses per week was as efficacious as weekly treatment doses, but with a higher degree of inflammation. Complete responses were achieved in smaller tumors, consistent with prior studies, suggesting that these are ideal candidates to evaluate in a clinical setting.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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