Introduction

Electrochemotherapy (ECT) is an approved treatment for local control of accessible tumor nodules. Recently, calcium electroporation (ECaT) has shown efficacy in clinical trials in humans and in vet species. Nonetheless, ECT/ECaT results in no impact on inaccessible, distant metastases, thus resulting in no significant effects on patients’ overall survival. ECT/ECaT can activate the immune system. However, this issue has never been investigated in detail. Based on a similar technology, we have developed a genetic vaccination platform based on the use of muscle DNA electro-gene-transfer (DNA-EGT). Erb-eVax is a vaccine targeting the oncogene HER2/neu, overexpressed in breast cancer and canine osteosarcoma. Here, we hypothesize that standard ECT can induce a low, but detectable immune response against Tumor Associated Antigens (TAA) and that ECT and DNA-EGT can achieve synergic effects.

Methods

We have utilized a clinically validated device for veterinary electroporation called Vet-ePorator, based on Cliniporator technology utilized and approved in Europe for ECT/ECaT applications and adapted to EGT. Mice challenged with a breast cancer cell line overexpressing HER2 were treated with ECT/ECaT, DNA-EGT or their combination. Dogs with metastatic breast cancer or osteosarcoma are currently being treated with ECT and/or Erb-eVax. All studies have been approved by Internal Ethics Committee for the research.

Results

ECT and ECaT induced a detectable cell-mediated immune response against HER2/neu and transient control of tumor growth. DNA-EGT was able to delay tumor growth over time whereas the combination ECT/DNA-EGT resulted in complete tumor rejection. ECT reduced tumor masses and Erb-eVax induced cell mediated and antibody immune responses against HER2/neu in treated dogs.

Conclusions

Our findings provide new data on tumor immunobiology and most importantly improve the efficacy of ECT/ECaT.

Clinical Significance of the Results

Novel immunotherapeutic approaches with a significant impact on patient’s survival and quality of life.

Abbreviations and drug names: Erb-eVax, calcium, bleomycin