Electroporation and Immunotherapy—Unleashing the Abscopal Effect

Abstract

The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic cancer, respectively. Interestingly, the treatment modalities have been shown to elicit immunogenic cell death, which in turn can induce an immune response towards the tumor cells. With the dawn of the immunotherapy era, the potential of combining ECT and IRE with immunotherapy has led to the launch of numerous studies. Data from the first clinical trials are promising, and new combination regimes might change the way we treat tumors characterized by low immunogenicity and high levels of immunosuppression, such as melanoma and pancreatic cancer. In this review we will give an introduction to ECT and IRE and discuss the impact on the immune system. Additionally, we will present the results of clinical and preclinical trials, investigating the combination of electroporation modalities and immunotherapy.

Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

“…Combination of the bystander effect in vitro induced by bleomycin electrotransfer and calcium electroporation suggested a possibility of a combination of these effects in vivo. We also hypothesized that in in vivo settings, the bystander effect can operate not only on neighboring cells but also modulate the immune response and induce an abscopal effect as suggested by other studies [ 45 , 46 ]. Indeed, we have observed the abscopal effect of combined bleomycin electrotransfer and calcium electroporation treatment both at 1200 and 1500 V/cm pulse application ( Figure 6 ).…”

“…The mechanism of action of the abscopal effect is closely related to the immune system of the treated organism [ 45 ]. Since IL-2 is known to increase sensitivity and proliferation of natural killer (NK) cells and cytotoxic T cells [ 47 ], we decided to monitor changes of this cytokine concentration in serum following abscopal effect inducing electroporation-based treatments.…”

“…Nevertheless, a clear mechanism of these effects is unknown, showing the need of more systemic investigations. Possible directions can be drawn from very recent reviews on interaction of EP-based therapies and immune response [ 45 , 65 ].…”

The induction of SARS-CoV-2-specific CD8+ T cell immunity uncouples with the viral spread in K18-hACE2 infected mice

“…Data from the experiment carried out three months after vaccine boosting excluded possible biases due to a general transient immune hyper-activation consequence of electroporation procedures 9 , and/or DNA loading. Additional confounding effects not related to Spike-specific vaccination can be also excluded considering the similar results obtained in Spikevax vaccinated mice.…”

“…Persistent Spike-specific CD8 + T cell immunity and block of virus replication in vaccinated mice three months after boosting. Electroporation procedures have the potential to induce a both localized and transient immune activation 9 . Hence, it was mandatory to evaluate possible influences of both the timing of infection after boosting and the method of vaccination on the prompt generation of the virus-specific CD8 + T cell immune response we observed in vaccinated/infected mice.…”