Treatment of invasive retinoblastoma in a murine model using an oncolytic picornavirus.
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.
Wadhwa
Lalita
L
Texas Children's Cancer Center, 6621 Fannin Street, M.C. 3-3320, Houston, TX 77030, USA.
Hurwitz
Mary Y
MY
Chévez-Barrios
Patricia
P
Hurwitz
Richard L
RL
D000818:Animals; D001932:Brain Neoplasms / Q000556:secondary / Q000628:therapy; D016543:Central Nervous System Neoplasms / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D050504:Oncolytic Viruses / Q000235:genetics*; D010849:Picornaviridae / Q000235:genetics*; D012175:Retinoblastoma / Q000628:therapy*; D016896:Treatment Outcome