Response of Retinoblastoma with Vitreous Tumor Seeding to Adenovirus-Mediated Delivery of Thymidine Kinase Followed by Ganciclovir
Abstract
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 10 8 viral particles (vp) had resolution of the tumor seeds around the injection site. The seven patients who were treated with doses ≥ 10 10 vp had resolution of their vitreous tumor seeds documented by fundoscopy. Toxicity included mild inflammation at 10 10 vp and moderate inflammation, corneal edema, and increased intraocular pressure at 10 11 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. 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.
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In a retinoblastoma cohort of eight patients, five developed ocular inflammation despite no measurable humoral or cellular immune response.
“The retinoblastoma cohort consisted of eight patients, five of whom developed ocular inflammation even though there was no measurable humoral or cellular immune response [65].”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [65]
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- Authors
- Chévez-Barrios, P., Chintagumpala, M., Mieler, W., Paysse, E., Boniuk, M., Kozinetz, C., Hurwitz, M. Y., & Hurwitz, R. L.
- Affiliations
- From 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
- Houston Methodist (US)
- Venue
- Journal of Clinical Oncology
- Published
- 2005-11-01
- Volume
- 23
- Issue
- 31
- Pages
- 7927-7935
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2166510225
- Cited by
- 143
- References
- 32
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 9 · 2016: 4 · 2015: 10 · 2014: 7 · 2013: 5 · 2012: 10
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R21CA097762, CA97762)
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- retinoblastoma, adenoviral vector, herpes simplex thymidine kinase, ganciclovir, suicide gene therapy, gene therapy toxicity, pediatric retinoblastoma, intravitreal injection, dose escalation
- MeSH terms
- Adenoviruses, Human, Antiviral Agents, Child, Combined Modality Therapy, Feasibility Studies, Genetic Vectors, Humans, Neoplasm Recurrence, Local, Neoplasm Seeding, Retinoblastoma, Thymidine Kinase, Vitreous Body, Genetic Therapy, Ganciclovir, Gene Transfer Techniques, Retinal Neoplasms
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