Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

Simple Summary The delivery of electric field to tumor cells or nodules induces cell electroporation that allows intracellular delivery of cytotoxic agents and eventually inhibits tumor growth. In this study, we showed that intracellular delivery of calcium ions and anticancer drug bleomycin not only kills the cells but also has a negative bystander effect on indirectly treated cells. We also showed that, when directly applied to one tumor, these treatments can inhibit the growth of a second, non-electroporated tumor. Electroporation-based antitumor therapies, including bleomycin electrotransfer, calcium electroporation, and irreversible electroporation, are very effective on directly treated tumors, but have no or low effect on distal nodules. In this study, we aimed to investigate the abscopal effect following calcium electroporation and bleomycin electrotransfer and to find out the effect of the increase of IL-2 serum concentration by muscle transfection. The bystander effect was analyzed in in vitro studies on 4T1tumor cells, while abscopal effect was investigated in an in vivo setting using Balb/c mice bearing 4T1 tumors. ELISA was used to monitor IL-2 serum concentration. We showed that, similarly to cell treatment with bleomycin electrotransfer, the bystander effect occurs also following calcium electroporation and that these effects can be combined. Combination of these treatments also resulted in the enhancement of the abscopal effect in vivo. Since these treatments resulted in an increase of IL-2 serum concentration only in mice bearing one but not two tumors, we increased IL-2 serum concentration by muscle transfection. Although this did not enhance the abscopal effect of combined tumor treatment using calcium electroporation and bleomycin electrotransfer, boosting of IL-2 serum concentration had a significant inhibitory effect on directly treated tumors.

Automated summary

This study shows that intracellular delivery of calcium ions and anticancer drug bleomycin not only kills the cells but also has a negative bystander effect on indirectly treated cells. These treatments are effective on directly treated tumors but have little effect on distal nodules. Combination with other methods is needed for the treatment of distal nodules.