Treatment of experimental osteosarcoma tumors in rat by herpes simplex thymidine kinase gene transfer and ganciclovir.

Previous results have demonstrated the efficiency of Herpes simplex type 1 thymidine kinase (HSV1-TK) retroviral gene transfer and ganciclovir (GCV) treatment of a human osteosarcoma cell line resulting in the death of the cell population and a proximal bystander effect; therefore, we investigated gene therapy on an in vivo osteosarcoma rat model. For in vivo experiments, small fragments of tumor were grafted onto rats in a paratibial position. Seven days after the graft, packaging cells (psi CRIP-TK and psi CRIP-LLZ) were inoculated into tumor mass, followed by GCV administration. In vivo results showed the efficiency of this system that allowed the reduction of the tumor mass and prevented lung metastasis appearance, which represents the normal evolution. This type of treatment seems promising for rapidly proliferating tumors such as osteosarcoma; the lower IC50 makes this system particularly attractive as clinically doses may be of low magnitude to prevent secondary effects in patients.