Nanosecond Pulsed Field Ablation in Oncology

Abstract

Cancer therapy has evolved significantly over the past three decades and this review focuses on some of the new ablation modalities that have been developed as well as the importance of combination therapies which enlist the immune system. During the late 1990’s various immune system checkpoints were discovered, and inhibitors of those immune checkpoints were found to boost the immune system enough in some patients to eliminate metastases. This revealed the power of the immune system to attack and eliminate tumors. However, for most patients simply inhibiting the immune checkpoints was insufficient and additional therapies were required. Current approaches involve ablation of the primary tumor followed by stimulation of the immune system to pick up tumor antigens released by the ablation and generate cytotoxic CD8+ T-cells to eliminate metastases. Tumor ablation involves the targeted delivery of either thermal or nonthermal energy sufficient to kill the tumor cells. Thermal ablation modalities were the first to be used but recent data suggest that the immune system is more strongly recruited by nonthermal modalities which have the additional advantage of sparing acellular structures such as neighboring nerves and blood vessels. We reviewed two studies that compared the efficacy of thermal with that of nonthermal ablation and concentrate on our progress using nanosecond pulsed field ablation. Recent studies that combine ablation with the injection of immune stimulants have shown that combination therapies are the most effective. Combining nsPFA with the intratumoral injection of immune stimulants boosts the immune system sufficiently to eliminate untreated tumors or metastases. We review the immune stimulants currently being used in preclinical studies and summarize the two clinical studies conducted thus far using nanosecond pulsed field ablation (nsPFA).