title: Absence of systemic immune response to adenovectors after intraocular administration to children with retinoblastoma.
abstract: The ocular environment has been shown to induce tolerance to locally administered antigens. We therefore investigated whether there was a systemic immune response against adenoviral vectors injected into the vitreous of retinoblastoma patients enrolled in a phase 1 clinical trial of adenoviral-mediated thymidine kinase gene transfer. Sections of enucleated eyes were immunostained with antibodies against inflammatory cells. A trend toward 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 (CTLs) or in adenovirus neutralizing antibodies. Therefore, in contrast to studies showing significant immunogenicity of Ad-RSVtk 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.
authors.affiliation: Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Cristhian J
authors.initials: CJ
authors.lastname: Ildefonso
authors.forename: Lingkun
authors.initials: L
authors.lastname: Kong
authors.forename: Ann
authors.initials: A
authors.lastname: Leen
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Chai
authors.forename: Veronica
authors.initials: V
authors.lastname: Petrochelli
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Mary Y
authors.initials: MY
authors.lastname: Hurwitz
authors.forename: Patricia
authors.initials: P
authors.lastname: Chévez-Barrios
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hurwitz
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D005123:Eye / Q000276:immunology / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008264:Macrophages / Q000276:immunology; D012175:Retinoblastoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D013937:Thymidine Kinase