Pulsed electric field activates immune system better than radiofrequency ablation
Local delivery of pulsed electric field (PEF) ablation slowed tumor response and had a better immune response when compared with traditional radiofrequency ablation (RFA) in a murine model. Partial tumor ablation was used to distinguish the benefits produced by the immune system between the two ablation modalities.
The findings of featured abstract “Pulsed Electric Field (PEF) Ablation Invokes Stronger Immune Cytokine Profile and Tumor Response than Radiofrequency Thermal Ablation for Matched Ablation Volumes” will be presented during Scientific Session 1, Ablation 1, Sunday, March 5, 3 p.m. in Room 221AB of the Phoenix Convention Center.
“The scope of this study was to deliver a partial ablation to understand the postablation biological cascade differences between thermal ablation and PEF, which does not depend on thermal processes to kill cells. To elucidate the differences between the methods, we looked at cell cytokine expression, immune cell infiltration and tumor response (including contralateral rechallenge),” explained presenting author Chiara Pastori, PhD, associate director of research at Galvanize Therapeutics. “If you can treat the whole tumor, that’s great, but if you cannot ablate 100 percent … you’re still activating the immune system.”
Thirty female mice were divided into sham, PEF and RFA—10 mice in each group—and injected with breast cancer tumor cells. In the nonsham groups, the researchers ablated approximately 80 percent of each tumor. After ablation, the researchers conducted histological analysis of the ablation zone and tumor growth, flow cytometry and serum cytokine analysis to understand the postablation biological cascades.
While RFA-treated tumors showed immune cells accumulating at the tumor–treatment zone boundary, PEF-treated tumors showed immune cell infiltration throughout the tumor. In addition, PEF treatment slowed tumor growth compared with RFA or sham treatments. Ingenuity Pathway Analysis of 32 serum cytokines revealed the most notable differences between groups on day 4 post ablation.
“Serum and tumor tissue cytokine analysis uncovered different immune responses: PEF-treated tumors were observed to have a greater recruitment of dendritic cells than RFA treated tumors,” Dr. Pastori said. “Moreover, we observed an increase in circulating adaptive immune cells in the blood of mice treated with PEF. This observation was inversely correlated with tumor volume—increased numbers of adaptive immune cells resulted in lower tumor volumes in PEF-treated mice.”
The cytokines analyses in the tumor and serum also suggest that PEF is associated with decreased accumulation of myeloid derived suppressor cells, decreased proliferation of tumor-associated macrophages, and decreased proliferation, survival and invasion of tumor cells, she said.
The findings show that not all ablation modalities are treated equal: “Local delivery of PEF demonstrates a systemic response, greater suppression of tumor growth and possibly superior synergy with checkpoint inhibitor immunotherapy compared to traditional RFA,” Dr. Pastori said.
The potential to generate a systemic immune response from a local therapy opens several new avenues for treatment, she said. “For example, in patients with presumed metastatic disease, PEF could be delivered at the time of the diagnostic biopsy to synergize and potentially enhance the response to standard-of-care pharmacotherapeutic agents while avoiding a second procedure. In addition, some patients may experience abscopal effects triggered by the PEF cell-killing mechanism and the resultant antigen release and immune stimulation that acts systemically to yield beneficial off-target effects.”
The Galvanize Aliya Pulsed Electric Field system is 510k cleared for the surgical ablation of soft tissue with a single monopolar 19-gauge 20 cm needle and is available in several leading centers across the United States. In addition, Galvanize Therapeutics is sponsoring several clinical trials focused on understanding the safety and clinical utility of Aliya PEF within standard of care algorithms for multiple malignancies with high unmet clinical needs. Aliya PEF uses nonthermal, short-duration electrical pulses to destabilize cellular integrity and disrupt homeostasis, leading to immunogenic cell death that has been shown previously to activate the immune system in both pre-clinical cancer models and human clinical trials of primary resectable non-small cell lung cancer.
