Oncolytic plasmid: A novel strategy for tumor immuno-gene therapy.

The oncolytic virus is expected to proliferate in and destroy tumor cells. The virus is also thought to generate antitumor immunity. Virally infected tumor cells express viral antigens on their surfaces. Such tumor cells or their fragments would be taken up by antigen-presenting cells (APCs) together with tumor-associated antigens (TAAs), and facilitated cross-priming of tumor-specific T cells. Virus-specific protein presented on the infected cells therefore played a crucial role in the enhancement of the adaptive antitumor immunity. In this study, a plasmid encoding adenovirus protein, the adenovirus death protein (ADP), was constructed, and a very fine complex of the plasmid with polyethylenimine (PEI) and chondroitin sulfate (CS) was injected into tumor-bearing mice. Transfection of the ADP gene was shown to suppress tumor growth as effectively as granulocyte-macrophage colony-stimulating factor (GM-CSF) transfection. When mice were administered plasmid coding ADP (pDNA-ADP) to generate an immune response to ADP prior to therapy, transfection of the ADP gene induced a much higher level of tumor growth suppression than that found in the non-immunized mice. An evident synergistic effect of ADP and GM-CSF genes was also observed, and at a pDNA-ADP/pDNA-GM-CSF ratio of 4:1, significant suppression of tumor growth was achieved even in the non-immunized mice.