IN-VITRO AND IN-VIVO ANTITUMOR EFFECTS OF RETROVIRUS-MEDIATED HERPES-SIMPLEX THYMIDINE KINASE GENE-TRANSFER IN HUMAN MEDULLOBLASTOMA

Herpes simplex virus thymidine kinase gene (HSVtk) transfer together w ith treatment with the prodrug ganciclovir (GCV) represents the most c ommonly used suicide gene approach for the gene therapy of human centr al nervous system malignancies. Despite encouraging results reported i n clinical trials conducted in adults, very little is known about the feasibility of this approach for the treatment of CNS tumors of childh ood. We studied the effects of the HSVtk/GCV system on human medullobl astoma cells in vitro and in vivo. The transfer of tk gene to medullob lastoma cells was capable of mediating cell suicide in vitro and in vi vo upon treatment with GCV, but the overall effect in vivo appeared to be suboptimal. The relatively low sensitivity of the medulloblastoma cells to viral infection and a limited bystander effect, coupled with a low expression of connexin-43 protein, might partially explain these results. Whether this is a peculiarity of the cell line studied or a general characteristic of medulloblastoma remains to be determined. Th ese findings should be taken into account for the future planning of g ene therapy trials for human medulloblastoma.