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Nonviral interferon alpha gene therapy inhibits growth of established tumors by eliciting a systemic immune response.

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.
AuthorsM Coleman, S Muller, A Quezada, S K Mendiratta, J Wang, N M Thull, J Bishop, M Matar, J Mester, F Pericle
JournalHuman gene therapy (Hum Gene Ther) Vol. 9 Issue 15 Pg. 2223-30 (Oct 10 1998) ISSN: 1043-0342 [Print] United States
PMID9794206 (Publication Type: Journal Article)
Chemical References
  • Interferon-alpha
  • Povidone
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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