April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Systemic Cellular and Humoral Immune Responses Are Absent After Intraocular Administration of Adenoviral Vectors to Children With Retinoblastoma
Author Affiliations & Notes
  • C. J. Ildefonso
    Translational Biol & Molecular Medicine,
    Baylor College of Medicine, Houston, Texas
  • A. M. Leen
    Center for Cell & Gene Therapy,
    Baylor College of Medicine, Houston, Texas
  • M. Y. Hurwitz
    Texas Children's Cancer Center,
    Baylor College of Medicine, Houston, Texas
  • P. Chevez-Barrios
    Pathology, Methodist Hospital, Houston, Texas
    Retinoblastoma Center of Houston, Houston, Texas
  • R. L. Hurwitz
    Texas Children's Cancer Center,
    Baylor College of Medicine, Houston, Texas
    Retinoblastoma Center of Houston, Houston, Texas
  • Footnotes
    Commercial Relationships  C.J. Ildefonso, None; A.M. Leen, None; M.Y. Hurwitz, None; P. Chevez-Barrios, None; R.L. Hurwitz, None.
  • Footnotes
    Support  Clayton Foundation for Research, Retina Research Foundation, Golfers Against Cancer, NIH Grants GM085793, DK064717, CA97762
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3135. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: gene transfer/gene therapy • adenovirus • immune tolerance/privilege 
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