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Journal of Clinical Oncology, Vol 23, No 31 (November 1), 2005: pp. 7927-7935 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.00.1883 Response of Retinoblastoma With Vitreous Tumor Seeding to Adenovirus-Mediated Delivery of Thymidine Kinase Followed by GanciclovirFrom the Departments of Pathology, Ophthalmology, and Pediatrics, Texas Children's Cancer Center; the Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital; and the Methodist Hospital, Houston, TX Address reprint requests to Richard L. Hurwitz, MD, Department of Pediatrics, Baylor College of Medicine, 6621 Fannin, MC 3-3320, Houston, TX 77030; e-mail: rhurwitz{at}bcm.edu PURPOSE: To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment for tumor seeds in the vitreous of children with retinoblastoma. PATIENTS AND METHODS: An Institutional Biosafety Committee–, Institutional Review Board–, Recombinant DNA Advisory Committee–, and US Food and Drug Administration–approved phase I study used intrapatient dose escalation of adenoviral vector containing a herpes simplex thymidine kinase gene (AdV-TK) followed by systemic administration of ganciclovir to treat bilateral retinoblastoma with vitreous tumor seeding refractory to standard therapies. Vitreous tumor seeds were treated by intravitreous injection of AdV-TK adjacent to disease sites. Each injection was followed by ganciclovir delivered intravenously every 12 hours for 7 days.
RESULTS: Eight patients with vitreous tumor seeds were enrolled. One patient who was treated with 108 viral particles (vp) had resolution of the tumor seeds around the injection site. The seven patients who were treated with doses CONCLUSION: AdV-TK followed by ganciclovir can be administered safely to children with retinoblastoma. Suicide gene therapy may contribute to the treatment of children with retinoblastoma tumor seeds in the vitreous, a resistant complication of retinoblastoma. National Institutes of Health Grant No. CA97762 defrayed costs of the viral vector and together with the Foundation for Research and Retina Research Foundation provided personnel support. National Institutes of Health Grant No. RR00188 and funding from the Texas Children's Hospital covered patient care expenses, and funding from the Fleming-Davenport Fund defrayed patient-transportation costs. Both P.C.-B. and M.C. contributed equally to this work. Presented in part at the annual Association for Research in Vision and Ophthalmology meeting April 25-29, 2004. Authors' disclosures of potential conflicts of interest are found at the end of this article.
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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1010 vp had resolution of their vitreous tumor seeds documented by fundoscopy. Toxicity included mild inflammation at 1010 vp and moderate inflammation, corneal edema, and increased intraocular pressure at 1011 vp. One patient was free of active vitreous tumor seeds 38 months after therapy. There has been no evidence of extraocular spread of tumor along the needle tract in any patient. 
