Adjuvant immunotherapy as a tool to boost effectiveness of electrochemotherapy

Abstract

Harnessing the body's own immune system to fight cancer is one of the most encouraging fields of cancer research today. Promising new cancer immunotherapies are currently being tested in preclinical and clinical trials, and a few have also reached regulatory approval. Likewise, the immunological properties of conventional therapies are being rediscovered and reinvestigated. It is now clear that the immune system is involved in antitumor action of most antitumor therapies. Special attention has been on different local ablative techniques, electrochemotherapy (ECT) being one of them. The main proposed mechanism of immunological involvement in the effectiveness of these therapies is their ability to induce an immunogenic form of cell death characterized by the release of tumor antigens from the therapy-killed cells in the context of a "danger signal," which can lead to formation of immune response against the released tumor antigens. Hence, ECT can be seen as an in situ vaccine. But since no systemic antitumor effects have been reported after ECT in clinical practice so far, this means that ECT monotherapy is not sufficient to overcome the tumor-tolerating immunosuppressive microenvironment of the tumor. Therefore, combining ECT with immunotherapy could be an efficient way to cure both the ECT-treated nodules and any distant nodule. In this chapter, the hypothesis of ECT as in situ vaccine will be present, putative adjuvants that could be, or already were, tested in combination with ECT will be listed, and the first clinical data for different combinations of ECT and immunotherapy that support the concept will be presented.