Pulsed Electric Fields (PEFs) are a focal ablation treatment that induces cell death without damaging the extracellular matrix, sparing sensitive structures. Its mechanism induces inflammatory signaling and affords viable antigen presentation within the tumor microenvironment. This preclinical study determines the immunogenic impact of PEF and whether its inclusion with anti-PD1 is beneficial.

Pulsed electric field (PEF) is an emerging technology being assessed for the cytoreductive treatment of tumors. PEF energy does not thermally denature proteins, allowing the release of intact tumor-associated antigens for antigen-presenting cells to drive a tumor specific response. This may promote an improved local response of the treated tumors and an abscopal effect. It remains to be proven whether this enhanced effect is related to an antigen-specific adaptive immune response. The Aliya System (Galvanize Therapeutics, GTI-00018 investigational device) is a biphasic, monopolar PEF system.

Introduction: Irreversible electroporation (IRE) employs multiple electrodes to induce tumor cell apoptosis within the ablation zone while sparing underlying tissue architecture. High-frequency IRE (HFIRE; ultrashort bipolar pulses) is an experimental alternative to existing IRE that obviates the need for paralytics or cardiac synchronization. We developed a novel, dual electrode-single needle (DESN) probe for HFIRE delivery, and evaluated efficacy in performing pancreatic ablations in vivo. Methods: Using a swine model the DESN-HFIRE probe was placed in the pancreatic head or tail and, in the absence of paralytics or cardiac synchronization, HFIRE ablations (2,250 V) were performed using 1-5-1, 2-5-2, or 5-5-5us (on-off-on) pulse configurations. Animals were maintained under anesthesia (6Hrs) prior to euthanasia and tissue recovery/evaluation. Results: All animals survived the experimental period and no EKG abnormalities or muscle spasm were observed during treatment. HFIRE delivery time was 5.4 ± 0.7mins and reproducible pancreatic ablations were created (903 ± 70 vs. 935 ± 148 vs. 2498 ± 3433 [1-5-1/2-5-2/5-5-5]), n = 4/setting). Histological analysis revealed clear demarcation between ablated-normal tissue, and preservation of underlying architecture within the ablation zone. Histochemistry and immunohistochemistry (caspase-3 activity) revealed electrically-induced necrosis (without thermal necrosis) adjacent to the probe, and extensive caspase-3 activity/apoptosis at the ablation-healthy tissue margin. Conclusions: H-FIRE delivery using a DESN probe rapidly and reproducibly ablated pancreatic tissue without significant thermal necrosis or the need for cardiac synchronization or intraoperative paralytics. Development, optimization, and testing of pulse parameter variations for SNDE-HFIRE may overcome the limitations and reservations associated with established IRE technology and increase the potential for use with minimally invasive approaches.

Background: Most pancreatic tumors are unresectable due to vascular involvement. Irreversible electroporation (IRE) uses multiple electrodes around the tumor to induce cellular apoptosis while sparing underlying tissue architecture. High frequency IRE (H-FIRE) is an experimental alternative to commercial IRE that obviates the need for muscle paralysis and cardiac synchronization. We have developed a novel, dual electrode-single needle (DESN) probe for H-FIRE delivery to enable single probe placement.