In Vivo gene transfer using implanted retroviral producer cells

A method of transferring in vivo a therapeutic gene into tumor cells in order to kill the tumor cells the method comprising:

• (a) introducing a retroviral vector into producer cells, wherein the producer cells comprise a provirus lacking a packaging signal required for encapsidation of RNA transcripts of the provirus into mature virus particles and wherein the retroviral vector comprises an intact packaging signal sequence, the retroviral vector having:
• (i) the therapeutic gene, and
• (ii) at least a second gene required for replication of the retrovirus into producer cells
• such that integration of a proviral DNA corresponding to the retroviral vector into the genome of the producer cells results in the generation of a modified retrovirus wherein at least one of the genes required for replication of the retroviral vector is replaced by the therapeutic gene
• (b) selecting producer cells ftom step (a) carrying the therapeutic gene;
• (c) grafting the producer cells in proximity to the dividing tumor cells in order to infect the tumor cells with the modified retrovirus being produced by the producer cells, thereby transfeing the therapeutic gene to the tumor cells;
• and
• (d) killing the tumor cells by administering a substance that is metabolized by the expression product of the therapeutic gene transferred to the tumor cells into a metabolite that kills the tumor cells.