| 摘要 |
In its broadest terms, the invention provides methods for the enhanced intracellular delivery of therapeutically active molecules to a target tumor cell. In a preferred embodiment, the method comprises providing engineered cells that express a heterologous nucleic acid that encodes a connexin and that contain a pro-drug activating gene, and contacting target tumor cells in a solid tumor with engineered cells that form functional gap junctions with said target tumor cells, such that the therapeutic molecule passes through a gap junction to a target tumor cell. More particularly, the invention involves providing engineered non-tumorigenic cells that express a first heterologous nucleic acid that encodes a connexin and a second heterologous nucleic acid that encodes a pro-drug activating molecule that converts a nontoxic substrate to a toxic metabolite, then contacting tumor cells in a solid tumor with engineered cells that form functional gap junctions with said tumor cells, and then exposing the engineered and tumor cells to the nontoxic substrate, whereby the nontoxic substrate is converted to the toxic metabolite in cells that expresses the pro-drug activating molecule, and the toxic metabolite then passes through gap junctions to adjacent coupled tumor cells, thereby inhibiting the cell growth of the tumor cells that contain the toxic metabolite. |
