Antimetastatic effects of electrochemotherapy and of histoincompatible interleukin-2-secreting cells in the murine Lewis lung tumor.

Abstract

Murine Lewis lung (3LL) tumors are characterized by the appearance of lung metastases after a regular period following their s.c. transplantation. We tested the respective efficiencies of various antitumor treatments: (i) electrochemotherapy (ECT), i.e. the systemic injection of bleomycin associated with electric pulses, locally delivered, that permeabilizes the tumor cells; (ii) intratumoral injection of histoincompatible cells that have been engineered in vitro to secrete high amounts of interleukin-2; and (iii) the combination of these two treatments. The growth of the s.c. transplanted tumors was followed up and the number of lung metastases was counted 14 days after the treatment. ECT alone resulted in the reduction of both the size of the tumor and the number of lung metastases. This latter effect can be partially explained by the effects of ECT on the s.c. tumor mass from which 3LL cells escape to colonize the lungs. The injection of IL-2-secreting cells alone had no effect on the s.c. mass and only a limited effect on the number of lung metastases. However, the combined treatment ECT plus IL-2-secreting cells resulted in antimetastatic effects potentiation that could result from stimulation of a non-specific immune response through an increase of NK activity.