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C. J. Ildefonso, A. M. Leen, M. Y. Hurwitz, P. Chevez-Barrios, R. L. Hurwitz; Systemic Cellular and Humoral Immune Responses Are Absent After Intraocular Administration of Adenoviral Vectors to Children With Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3135.
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The ocular environment has been shown to induce systemic tolerance to locally administered antigens. We therefore hypothesized that intraocular injection of adenoviral vectors into children with retinoblastoma would not elicit a measurable systemic immune response.
Enucleated eyes and peripheral blood samples were obtained from patients enrolled in a phase 1 clinical trial that evaluated the safety of administration of AdV-RSVtk to patients with retinoblastoma (Chévez-Barrios, et al J Clin Oncol 23:7927-7935, 2005). Inflammatory cells in sections of the enucleated eyes were detected by immunohistochemistry. Systemic cellular responses were evaluated using ELISPOT assays to detect adenovirus-specific cytotoxic T lymphocytes and humoral responses were measured by determining the presence or absence of adenovirus neutralizing antibodies in peripheral blood samples.
A trend towards increasing numbers of plasma cells, T-cells, macrophages and antigen presenting cells was observed in the injected subjects’ eyes, but systemically, there was no significant increase in the number of adenovirus-specific cytotoxic T lymphocytes or in adenovirus neutralizing antibodies.
Adenoviral vectors promote sustained transgene expression in the retina (Mallam, et al IOVS 45: 1680-1687, 2004). In contrast to studies showing significant immunogenicity of adenoviral vectors following injection into extraocular tumors, injection into the eye produces only a mild local inflammatory response without evidence of systemic cellular or humoral immune responses to adenovirus; therefore, these vectors may be acceptable for therapeutic gene delivery to humans with ocular disorders.
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