SYSTEMIC ANTITUMOR EFFECTS OF ELECTROCHEMOTHERAPY COMBINED WITH HISTOINCOMPATIBLE CELLS SECRETING INTERLEUKIN-2

Electrochemotherapy is an antitumor treatment that combines a cytotoxi c drug with the local administration of electric pulses delivered at t he tumor site. We previously found that in mice the cure rate of subcu taneous transplanted tumors treated by electrochemotherapy is increase d by repeated systemic interleukin-2 (IL-2) injections. Moreover, hist oincompatible cells engineered to secrete IL-2 allow the rejection of syngeneic tumor cells when both cells are inoculated together. In this study of preestablished tumors in mice we show that after electrochem otherapy, delayed peritumoral injections of histoincompatible IL-2-pro ducing cells result in the cure of almost all the tumors. Moreover, th is combined local treatment leads to cures of untreated, contralateral ly transplanted tumors. This systemic antitumor immunity also resulted in complete protection of the cured mice against further inocula of t he tumor cells, These results, which were obtained using allogeneic as well as xenogeneic IL-2-secreting cells, suggest that electrochemothe rapy combined with such cellular immunotherapy might be a useful appro ach for the treatment of metastasizing cancers.