Immunostimulatory effects of nanosecond pulsed electric fields

Abstract Intense pulsed electric fields (PEF) are increasingly employed for tumor ablation, including inoperable tumors, bleeding metastases, and tumors unresponsive to alternative treatments. PEF disrupt the membrane barrier of cells leading irreversible changes in homeostasis cell death. Using different models, we found that treatment with nanosecond duration (nsPEF) enhance host antitumor immune response. The strongest effect was measured mice bearing CT26 colon carcinoma where local nsPEF protected 78% animals from a second challenge. We hypothesize nsPEF-treated act as an in-situ cancer vaccine by initiating innate immunity while molding sustaining adaptive immunity. Indeed, provide evidence damage created these short electrical stimuli is sensed platform known inflammasome. Upon assembly, inflammasome induces proinflammatory cytokine processing form death pyroptosis. triggered pyroptosis macrophages accompanied caspase-1 activation release IL-1β. Concurrently, sustain immunity, activate persistent ER-stress phosphorylation translation initiation factor 2α (eIF2α): biomarker immunogenic Tumor antigen-release comes damage-associated molecular patterns such ATP, HMGB1 calreticulin. Understanding manipulating cross talk between after expected improve immunotherapeutic response Pulse Biosciences, Inc.