GENE-THERAPY OF SPONTANEOUS CANINE MELANOMA AND FELINE FIBROSARCOMA BY INTRATUMORAL ADMINISTRATION OF HISTOINCOMPATIBLE CELLS EXPRESSING HUMAN INTERLEUKIN-2

The production of human interleukin-2 (hIL-2) local to the tumor site by engineered histoincompatible cells has been shown in various murine models to promote a strong immune response leading to tumor growth in hibition or rejection. To assess whether this strategy would be simila rly applicable for treatment of primary neoplastic cells, two naturall y occurring tumors were used as preclinical models: the highly metasta tic melanoma of the dog and the low metastatic fibrosarcoma of the cat . We demonstrate that both cats and dogs when treated by tumor surgery , radiotherapy and repeated local injections of xenogeneic Vero cells secreting high levels of hIL-2 relapse less frequently and survive lon ger than control animals treated by surgery and radiotherapy alone. Lo cal secretion of hIL-2 by the xenogeneic cells is shown to be necessar y for the induction of an optimal antitumor effect. Moreover, the safe ty of the procedure was demonstrated in both animal models and through extensive toxicological analysis performed in rats. These results con firm for the first time to our knowledge the safety and therapeutic po tential of a gene transfer strategy in animals with spontaneous metast atic and nonmetastatic tumors.