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Antitumor Effects of Interferon-: In Vivo Therapy of Human Tumor Xenografts in Nude Mice

Vical, Inc., San Diego, California 92121

The antitumor effect of the type I IFN, IFN-, was evaluated in both in vitro and in vivo studies of human cancer. For these studies, the cDNA for human IFN- was cloned into a eukaryotic expression plasmid DNA (pDNA) driven by the cytomegalovirus promoter. Supernatants from UM449 cells transfected in vitro with IFN- pDNA had antiproliferative effects on 11 of 13 human tumor cell lines. For in vivo studies, nude mice were implanted s.c. with one of the following human tumors: NIH:OVCAR-3 ovarian carcinoma, A375 melanoma, or A431 epidermoid carcinoma. Direct intratumoral injection of 100 µg of a IFN- pDNA DMRIE/DOPE complex (1:1 DNA:DMRIE mass ratio) for 6 consecutive days resulted in a significant reduction in the tumor volume of NIH:OVCAR-3 ovarian carcinoma or A375 melanoma (P = 0.02). IFN- pDNA delivered by i.m. injection also had an antitumor effect. Nude mice bearing s.c. A431 epidermoid carcinoma and injected i.m. with 100 µg of IFN- pDNA, twice per week for 3 weeks, had a significant reduction in tumor volume (P = 0.009). These results demonstrate for the first time that IFN- can have in vivo antitumor effects in several models of human cancer.

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