AN ADENOVIRAL VECTOR EXPRESSING INTERLEUKIN-4 MODULATES TUMORIGENICITY AND INDUCES REGRESSION IN A MURINE BREAST-CANCER MODEL
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Anti-tumor activity of a recombinant adenovirus expressing murine IL-4 (AdCAIL-4) was investigated in a murine model of mammary adenocarcinoma. Primary tumor cells derived from mammary adenocarcinomas induced in transgenic mice by the middle T antigen gene of polyomavirus were infected with AdCAIL-4 and injected into syngeneic non-tumor bearing recipients. Expression of IL-4 by AdCAIL-4 transduced tumor cells significantly prolonged survival of all animals and prevented tumor development in 61% of recipient mice. When tumor bearing animals were injected intra-tumorally with AdCAIL-4, all animals survived at least 8 to 10 weeks longer than controls, and 50% of treated animals underwent complete tumor regression. Both en: vivo and in vivo treatment with AdCAIL-4 resulted in infiltration by eosinophils in and around the tumor site. Animals which had undergone complete tumor regression were protected from a second challenge suggesting that immunotherapy with Ad vectors expressing cytokines may protect from metastatic disease.
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