Adenovirus mediated gene therapy for retinoblastoma

Purpose. These studies were designed to provide preclinical efficacy data for adenovirus mediated gene therapy protocols for the treatment of retinoblastoma. Methods. To develop an animal tumor model, cultured cells derived from a human retinoblastoma (Y79) were injected into the posterior chamber of the eyes of immuno-deficient mice. The infectivity of replication deficient adenovirus (AD) containing either the E. coli β-galactosidase (LacZ) gene or the HSV thymidine kinase (TK) gene was first examined in vitro using Y79 cells. β-galactosidase expression was evidenced by the appearance of blue staining after incubation with X-gal. The Y79 cells infected with AD/TK were treated with the antiviral drug ganciclovir and the viability of the cells was determined. The tumors induced by Y79 injections in the mice were infected with AD/LacZ and the β-galactosidase expression was determined by X-gal staining. Results. AD/LacZ is capable of infecting Y79 cells and retinoblastoma tumors generated in mice injected with Y79 cells; β-galactosidase activity was detectable both in vitro and in vivo. AD/TK infection and ganciclovir treatment effectively killed Y79 cells in vitro. Conclusions. AD/TK infection followed by ganciclovir treatment may provide an effective therapy for retinoblastoma.