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Establishment and Propagation of Human Retinoblastoma Tumors in Immune Deficient Mice
Published on: August 4, 2011
Treatment of invasive retinoblastoma in a murine model using an oncolytic picornavirus
Lalita Wadhwa1, Mary Y Hurwitz, Patricia Chévez-Barrios
1Texas Children's Cancer Center, 6621 Fannin Street, M.C. 3-3320, Houston, TX 77030, USA.
Abstract:
Retinoblastoma, the most common intraocular malignancy of childhood, metastasizes by initial invasion of the choroid and the optic nerve. There is no effective treatment for metastatic retinoblastoma, especially when the central nervous system (CNS) is involved, and prevention of this complication is a treatment priority. Seneca Valley Virus (SVV-001) is a conditionally replication-competent picornavirus that is not pathogenic to normal human cells but can kill human retinoblastoma cells in vitro with an IC(50) of <1 viral particle (vp) per cell. A xenograft murine model of metastatic retinoblastoma was used to examine the therapeutic potential of SVV-001. Histopathologic analysis of ocular and brain tissues after a single tail vein injection of SVV-001 (1 x 10(13) vp/kg) showed effective treatment of choroid and ocular nerve tumor invasion (1 of 20 animals with invasive disease in the treated group versus 7 of 20 animals with invasive disease in the control group; P = 0.017) and prevention of CNS metastasis (0 of 20 animals with CNS metastatic disease in the treated group versus 4 of 20 animals with CNS disease in the control group; P = 0.036). There were no observed adverse events due to the virus in any of the treated animals. SVV-001 may be effective as a treatment of locally invasive and metastatic retinoblastoma.
Insights
Seneca Valley Virus (SVV-001) effectively treats and prevents metastasis in retinoblastoma, a childhood eye cancer. This novel oncolytic virus shows promise for treating invasive and metastatic retinoblastoma with no observed adverse effects.
Area of Science:
- Oncology
- Virology
- Pediatric Malignancy
Background:
- Retinoblastoma is the most common childhood intraocular cancer.
- Metastasis to the choroid, optic nerve, and central nervous system (CNS) is a primary concern.
- Effective treatments for metastatic retinoblastoma, particularly with CNS involvement, are lacking.
Purpose of the Study:
- To evaluate the therapeutic potential of Seneca Valley Virus (SVV-001) in a murine model of metastatic retinoblastoma.
- To assess SVV-001's efficacy in treating local invasion and preventing CNS metastasis.
Main Methods:
- A xenograft murine model of metastatic retinoblastoma was utilized.
- Animals received a single tail vein injection of SVV-001 (1 x 10(13) vp/kg).
- Histopathologic analysis of ocular and brain tissues was performed to assess tumor invasion and metastasis.
Main Results:
- SVV-001 significantly reduced choroid and optic nerve tumor invasion (P = 0.017).
- SVV-001 prevented central nervous system (CNS) metastasis (P = 0.036).
- No adverse events were observed in animals treated with SVV-001.
Conclusions:
- SVV-001 demonstrates therapeutic potential for locally invasive retinoblastoma.
- SVV-001 may be an effective preventative treatment against CNS metastasis in retinoblastoma.
- SVV-001 is a promising candidate for treating metastatic retinoblastoma.

