Local Delivery of Therapeutic Proteins by Intratumoral Injection of Plasmid DNA-Lipid Complexes

There are several strategies by which one may deliver a plasmid DNA (pDNA) encoding a therapeutic gene to a tumor. One may transfect cells ex vivo, single cell clone, expand the clone in vitro, and reinject the cells at the tumor site. This is a labor-intensive process and is especially impractical for human tumor therapy. Another method is intramuscular (im) injection of the therapeutic pDNA to achieve circulating levels of the protein (discussed in Chapter 14 by Horton and Parker). A third method is to directly inject the therapeutic pDNA into the tumor. For accessible neoplasms, this is a simple procedure, and can be useful for delivery of a therapeutic gene, such as a cytokine gene, to the tumor site. Using this technique, one may achieve high local levels of a therapeutic protein, yet have low systemic levels, thereby reducing side effects (1,2). In addition, producing a cytokine locally may attract immune cells to the tumor site and promote an antitumor immune response (1-3). Furthermore, certain cytokines may be more effective when delivered locally, rather than systemically (Horton, unpublished results).