| First Author | Coleman M | Year | 1998 |
| Journal | Hum Gene Ther | Volume | 9 |
| Issue | 15 | Pages | 2223-30 |
| PubMed ID | 9794206 | Mgi Jnum | J:50683 |
| Mgi Id | MGI:1309581 | Doi | 10.1089/hum.1998.9.15-2223 |
| Citation | Coleman M, et al. (1998) Nonviral interferon alpha gene therapy inhibits growth of established tumors by eliciting a systemic immune response. Hum Gene Ther 9(15):2223-30 |
| abstractText | 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. |
