Abstract |
A plasmid expression system encoding murine IFN-alpha4 and complexed with a protective interactive noncondensing polymeric (PINC) delivery system was used for in vivo immunotherapy treatment of an immunogenic murine renal cell carcinoma, Renca, and a nonimmunogenic mammary adenocarcinoma, TS/A. Mice bearing established tumors were treated with IFN-alpha/ polyvinylpyrrolidone (PVP) expression complexes via direct intratumoral injection. Up to 100% inhibition of tumor growth was observed in the treated mice. By using an optimal dose of 96 and 48 microg of formulated IFN-alpha plasmid for the treatment of Renca and TS/A, respectively, 30% (Renca) and 10% (TS/A) of the treated animals remained tumor free. Inhibition of tumor growth was dependent on activation of the immune system. The antitumor activity elicited by IFN-alpha gene therapy was abrogated when mice were selectively depleted of CD8+ T cells. By contrast, depletion of CD4+ T cells resulted in enhanced tumor rejection following IFN- alpha/PVP treatments. Finally, mice that remained tumor free following IFN-alpha gene therapy displayed immune resistance to a subsequent tumor challenge. These data provide evidence that IFN-alpha gene therapy can be used to induce an efficient antitumor response in vivo.
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Authors | M Coleman, S Muller, A Quezada, S K Mendiratta, J Wang, N M Thull, J Bishop, M Matar, J Mester, F Pericle |
Journal | Human gene therapy
(Hum Gene Ther)
Vol. 9
Issue 15
Pg. 2223-30
(Oct 10 1998)
ISSN: 1043-0342 [Print] United States |
PMID | 9794206
(Publication Type: Journal Article)
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Chemical References |
- Interferon-alpha
- Povidone
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Topics |
- Adenocarcinoma
(immunology, therapy)
- Animals
- Blotting, Western
- CD8-Positive T-Lymphocytes
(immunology)
- Carcinoma, Renal Cell
(immunology, therapy)
- Female
- Genetic Therapy
(methods)
- Interferon-alpha
(genetics, immunology)
- Kidney Neoplasms
(immunology, therapy)
- Mammary Neoplasms, Experimental
(immunology, therapy)
- Mice
- Mice, Inbred BALB C
- Neoplasms, Experimental
(immunology, therapy)
- Plasmids
(genetics)
- Povidone
- Tumor Cells, Cultured
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