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Effective Genetic Therapy of Established Medullary Thyroid Carcinomas with Murine Interleukin-2: Dissemination and Cytotoxicity Studies in a Rat Tumor Model¹

Thyroid Study Unit/MC 3090 (R.Z., L.J.D.), Department of Medicine, Department of Pathology (F.H.S.), The University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Leslie J. DeGroot, M.D., Thyroid Study Unit, Mail Code 3090, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637.

Replication-defective adenovirus (AdCMVmIL2) expressing murine interleukin-2 was directly injected into rat medullary thyroid carcinomas to examine antitumor activity. AdCMVmIL2 cured 42.9% of all treated tumor bearing animals. Most cured rats were protected against tumor growth after subsequent rechallenge with wild-type tumor cells, reflecting the immunity obtained from the original treatment. Studies of viral dissemination showed that the intratumoral inoculated viruses can enter the circulation, infect peripheral tissues, and express genes driven by the CMV promoter. Liver is the main target organ. In a toxicity study, AdCMVmIL2 was administered iv at a dose five times higher than that given directly into tumor. No detectable side effect was found. Histological studies showed variable degrees of lymphocyte infiltration in the livers of studied animals, and no functional change indicated by the normal serum level of glutamic oxalacetic transaminase and glutamic pyruvic transaminase was found in all animals studied. These data demonstrate that AdCMVmIL2 is an effective antitumor agent in this animal model, and that virus treatment can be given without significant toxicity to other organs.

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