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
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.
UR - http://www.scopus.com/inward/record.url?scp=77957587385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957587385&partnerID=8YFLogxK
U2 - 10.1038/mt.2010.139
DO - 10.1038/mt.2010.139
M3 - Article
C2 - 20606647
AN - SCOPUS:77957587385
VL - 18
SP - 1885
EP - 1890
JO - Molecular therapy : the journal of the American Society of Gene Therapy
JF - Molecular therapy : the journal of the American Society of Gene Therapy
SN - 1525-0016
IS - 10
ER -