Abstract
Immunotherapy is becoming a very common treatment for cancer, using approaches like checkpoint inhibition, T cell transfer therapy, monoclonal antibodies and cancer vaccination. However, these approaches involve high doses of immune therapeutics with problematic side effects. A promising approach to reducing the dose of immunotherapeutic agents given to a cancer patient is to combine it with electrical stimulation, which can act in two ways; it can either modulate the immune system to produce the immune cytokines and agents in the patient’s body or it can increase the cellular uptake of these immune agents via electroporation. Electrical stimulation in form of direct current has been shown to reduce tumor sizes in immune-competent mice while having no effect on tumor sizes in immune-deficient mice. Several studies have used nano-pulsed electrical stimulations to activate the immune system and drive it against tumor cells. This approach has been utilized for different types of cancers, like fibrosarcoma, hepatocellular carcinoma, human papillomavirus etc. Another common approach is to combine electrochemotherapy with immune modulation, either by inducing immunogenic cell death or injecting immunostimulants that increase the effectiveness of the treatments. Several therapies utilize electroporation to deliver immunostimulants (like genes encoded with cytokine producing sequences, cancer specific antigens or fragments of anti-tumor toxins) more effectively. Lastly, electrical stimulation of the vagus nerve can trigger production and activation of anti-tumor immune cells and immune reactions. Hence, the use of electrical stimulation to modulate the immune system in different ways can be a promising approach to treat cancer.
Highlights
Overall ViewImmunotherapy is emerging as a very promising approach for cancer treatment
The delivery of the mixed lineage kinase domain-like (MLKL)-Messenger RNAs (mRNAs) enhanced antitumor immunity against neoepitopes by activating CD8α+ dendritic cells and type I interferons (IFN). These results indicate that electroporation led to an efficient uptake of the MLKL-mRNA by the tumor cells and the effectiveness of the antitumor effects of the MLKL protein
We have described the use of electrical stimulation for immune modulation and engineering for the treatment of cancer
Summary
Ritopa Das 1, Sofia Langou 2, Thinh T. Immunotherapy is becoming a very common treatment for cancer, using approaches like checkpoint inhibition, T cell transfer therapy, monoclonal antibodies and cancer vaccination. These approaches involve high doses of immune therapeutics with problematic side effects. Several studies have used nano-pulsed electrical stimulations to activate the immune system and drive it against tumor cells This approach has been utilized for different types of cancers, like fibrosarcoma, hepatocellular carcinoma, human papillomavirus etc. Another common approach is to combine electrochemotherapy with immune modulation, either by inducing immunogenic cell death or injecting immunostimulants that increase the effectiveness of the treatments.
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