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

Cristhian J. Ildefonso, Lingkun Kong, Ann Leen, Samantha J. Chai, Veronica Petrochelli, Murali Chintagumpala, Mary Y. Hurwitz, Patricia Chévez-Barrios, Richard Hurwitz

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1885-1890
Number of pages6
JournalMolecular Therapy
Volume18
Issue number10
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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