Absence of systemic immune response to adenovectors after intraocular administration to children with retinoblastoma.
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.
Ildefonso
Cristhian J
CJ
Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA.
Kong
Lingkun
L
Leen
Ann
A
Chai
Samantha J
SJ
Petrochelli
Veronica
V
Chintagumpala
Murali
M
Hurwitz
Mary Y
MY
Chévez-Barrios
Patricia
P
Hurwitz
Richard L
RL
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
D013937:Thymidine Kinase