Abstract: The major problem with current direct delivery techniques of therapeutic reagents into solid tumors, especially of cells or large volumes of recombinant DNA reagents or drugs, has been resistance of the tissues to the influx of the fluid and/or cells, resulting in low quantities of the fluid and/or cells penetrating into and remaining in the tumor tissue to be treated. Increased penetration and/or reduced backflow and diversion through the point of entry, so that more material is introduced into and remains in the tumor, is obtained through the use of a viscous vehicle, most preferably having a similar density to tissue, for the material to be delivered. Preferred materials include solutions or suspensions of a polymeric material which gel or solidify at the time of or shortly after injection or implantation. In the preferred embodiment, the solution is injected via a catheter into regions of the tumor to be treated.

Abstract: 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.

Abstract: It has been discovered that cells such as genetically engineered fibroblasts and keratinocytes can be cultured in the cyst fluid of encapsulated tumors. This provides a means for proliferating genetically engineered producer cells within these types of tumors, increasing the number of cells producing viral particles, which then transduce the surrounding tumor cells with the genetic material, in the preferred embodiment, a lethal gene. A number of different tumor types form "cysts", which contain fluid produced by the tumor cells, including brain tumor cells such as gliomas, and many types of breast, and lung tumors. These cyst fluids have been shown to contain elevated levels of certain growth factors, for example, fibroblast growth factor (FGF) and epidermal growth factor (EGF).

Abstract: The major problem with current direct delivery techniques of therapeutic reagents into solid tumors, especially of cells or large volumes of recombinant DNA reagents or drugs, has been resistance of the tissues to the influx of the fluid and/or cells, resulting in low quantities of the fluid and/or cells penetrating into and remaining in the tumor tissue to be treated. Increased penetration and/or reduced backflow and diversion through the point of entry, so that more material is introduced into and remains in the tumor, is obtained through the use of a viscous vehicle, most preferably having a similar density to tissue, for the material to be delivered. Preferred materials include solutions or suspensions of a polymeric material which gel or solidify at the time of or shortly after injection or implantation. In the preferred embodiment, the solution is injected via a catheter into regions of the tumor to be treated.