TY - JOUR
T1 - Absence of systemic immune response to adenovectors after intraocular administration to children with retinoblastoma
AU - Ildefonso, Cristhian J.
AU - Kong, Lingkun
AU - Leen, Ann
AU - Chai, Samantha J.
AU - Petrochelli, Veronica
AU - Chintagumpala, Murali
AU - Hurwitz, Mary Y.
AU - Chévez-Barrios, Patricia
AU - Hurwitz, Richard
N1 - Funding Information:
This research was funded, in part, by NIH grants GM085793 (C.J.I.), CA103698 (R.L.H.), CA97762 (R.L.H.), Clayton Foundation for Research, Retina Research Foundation, Golfers Against Cancer, and the Howard Hughes Medical Institutes Med Into Grad Initiative.
PY - 2010/10
Y1 - 2010/10
N2 - 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.
AB - 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.
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U2 - 10.1038/mt.2010.139
DO - 10.1038/mt.2010.139
M3 - Article
C2 - 20606647
AN - SCOPUS:77957587385
SN - 1525-0016
VL - 18
SP - 1885
EP - 1890
JO - Molecular Therapy
JF - Molecular Therapy
IS - 10
ER -