Enhancement of the Anti-Tumor Immunity Following Tumor Ablation by Electrochemical Treatment

Background: Tumor ablation is a nonsurgical technique that is used to eradicate solid tumors. This strategy results in stimulating anti-tumor immunity against distant tumor cells by exposing the body to large amounts of tumor antigen. Pulsed Electric Current Tumor Ablation (PECTA) is an intratumoral treatment developed in our lab which destroys the tumor tissue, mainly by forming low and high pH areas and free radicals formation. In this study we examined the effects of PETCA treatment on primary tumor destruction, tumor recurrence, stimulation of anti-tumor immunity and survival. Moreover, we examined the ability to promote the anti-tumor immune response by either the immunoadjuvant, CpG, or the suppressor cells inhibitors; APCP (CD73 inhibitor), Sildenafil (PDE-5 inhibitor) and Cimetidine.

Methods: Tumors of breast adenocarcinoma (DA3), or fibrosarcoma (BLC25) cells, in Balb/c mice, were treated by PECTA or surgery. PECTA was applied by intratumoral electrodes delivering 75-100 coulombs per electrode per cm³ of tumor tissue (C/E/cm³). The efficacy of ablation and the development of anti-tumor responses were evaluated by survival monitoring and challenging the mice with secondary tumor cells.

Results: The charge of 100 C/E/cm³ was found as optimal for maximal elimination of primary tumors in DA3 model, whereas in BLC25 the optimal charge was 75 C/E/cm³. In addition, DA3 bearing mice cured by PECTA combined with CpG, APCP or Sildenafil were more resistant to the growth of a tumor cell challenge and survived longer than mice treated by surgery.

Conclusions: The findings indicate that PECTA efficiently eradicates breast adenocarcinoma and fibrosarcoma tumors. Furthermore, when combined with CpG, APCP or Sildenafil the treatment stimulates a protection against secondary tumor and distant metastases development and thus improves the survival.