Absence of systemic immune response to adenovectors after intraocular administration to children with retinoblastoma

Mol Ther. 2010 Oct;18(10):1885-90. doi: 10.1038/mt.2010.139. Epub 2010 Jul 6.


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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / immunology*
  • Antigen-Presenting Cells / immunology
  • Eye / immunology
  • Eye / metabolism
  • Genetic Therapy / methods
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Macrophages / immunology
  • Retinoblastoma / genetics
  • Retinoblastoma / immunology*
  • Retinoblastoma / metabolism
  • Retinoblastoma / therapy*
  • T-Lymphocytes / immunology
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism


  • Thymidine Kinase