Tumor Growth Inhibition in a Experimental Model of Human Uveal Melanoma: Genetic Therapy With Adenovirus H5 dl118

Abstract

Abstract: : Purpose: To assess the efficacy of mutant adenovirus therapy in an experimental model of human uveal melanoma in rabbits. Methods: A million cell suspension (92-1 human uveal melanoma cell line) previously infected by H5 dL118 adenovirus (Ad) was implanted in the suprachoroidal space of immunosuppressed rabbits with Cyclosporine A (15mg/kg/day). Two animal groups were studied. Experimental group (1): tumor cells were infected by Ads lacking the 19-kDa and 55-kDa E1B genes (20 Ads/cell). Control group (2): tumor cells were treated with PBS. Weight determination and funduscopic examination of the eye was performed weekly and general status assessment daily up to the end of the experiment. Animals were sacrificed at the end of eighth week and the eye was obtained for histopathologic examination. Tumors height, base, and total area in histologic sections were measured with a computerized imaging analysis system. Presence of extraescleral extension were analyzed. The survival curve was calculated by the Kaplan-Meier method. An exact method based in the binomial distribution was used to calculate differences between groups. Tumor height, base and area were compared between groups using Student t test after a logaritmic transformation of data. Results: No differences were found in weight, general status assessment and survival between groups. Infiltrative pigmented intraocular tumors were observed in 9 animals of group 1 and 13 of group 2 by funduscopic evaluation of the eye. Histopathologic examination of the tumors showed differences between both groups regarding tumor height, base and area. Moreover, extraocular extension were found in only 2 animals of group 1 and in 10 of group 2 (p< 0.05). Conclusion: Treatment with mutant adenovirus in this animal model is effective in decreasing the primary tumor area and extraocular extension rate. New Ad administration strategies and protocols should be tested to validate the usefulness of this new therapy in uveal melanoma.

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