Effective genetic therapy of established medullary thyroid carcinomas withmurine interleukin-2: Dissemination and cytotoxicity studies in a rat tumor model

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