The present invention is directed to methods of transferring therapeutic genes to brain tumor cells in order to kill the cells. In general, the method of the present invention comprises: (1) introducing a retrovirus containing a selectable marker and at least one gene required for its replication into producer cells such that integration of the proviral DNA corresponding to the retrovirus into the genome of the producer cell results in the generation of a modified retrovirus wherein at least one of the genes required for replication of the retrovirus is replaced by the therapeutic gene or genes; (2) selecting producer cells in which the modified retrovirus is incorporated as part of the genome of the producer cells; (3) grafting the producer cells in proximity to the dividing tumor cell in order to infect the tumor cell with the modified retrovirus, thereby transferring the therapeutic gene or genes to the tumor cell; and (4) killing the cells by administering a substance that is metabolized by the therapeutic gene transferred to the tumor cells into a metabolite that kills the cells. Suitable retroviral vectors and methods for generating them, producer cells, and grafting methods are described.
