| Autor: |
Santodonato, Laura, Ferrantini, Maria, Palombo, Fabio, Aurisicchio, Luigi, Delmastro, Paola, La Monica, Nicola, Di Marco, Stefania, Ciliberto, Gennaro, Du, Mark X, Taylor, Milton W, Belardelli, Filippo |
| Předmět: |
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| Zdroj: |
Cancer Gene Therapy; Jan2001, Vol. 8 Issue 1, p63, 10p |
| Abstrakt: |
Recent studies have shown that gene therapy with type I interferon (IFN) in an adenovirus vector is a powerful tool to suppress the growth of human tumors transplanted in immune-deficient mice. However, in these studies the host immune-mediated effects, which may be important in mediating the long-term control of tumor growth by these cytokines, was not studied. In this paper, we evaluate the antitumor efficacy of different adenoviral vectors containing mouse IFN-α genes (i.e., a first-generation replicationdefective vector containing IFN-α1 and two different second-generation vectors containing IFN-α2) in immunocompetent DBA/2 mice transplanted with highly metastatic Friend leukemic cells resistant in vitro to type I IFN. We found that injection of all the different adenovirus vectors containing mouse IFN-α genes resulted in a marked antitumor response in mice transplanted either subcutaneously or intravenously with IFN-resistant Friend leukemic cells compared to tumor-bearing animals inoculated with a control vector. Tumor growth inhibition after injection of IFN-adenovirus vectors was associated with a prolonged presence of high IFN levels in the sera of the injected mice. Suppression of metastatic tumor growth was also observed after a single injection of the IFN-adenovirus recombinant vectors, whereas a comparable antitumor response generally required several injections of high doses of IFN. Altogether, these results demonstrate that IFN-adenoviral vectors can efficiently inhibit metastatic tumor growth by hostmediated mechanisms and suggest that adenovirus-mediated IFN-α gene therapy may represent an attractive alternative to the conventional clinical use of this cytokine, which generally requires multiple injections of high IFN doses for a prolonged period of time. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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