A recent study comparing ablation technologies on murine cancer models indicates promising results for advanced biphasic pulsed electric field (PEF) ablation and may have achieved an improved post-ablation environment to induce the abscopal effect, according to researchers.
The study focuses on two cancer ablation technologies—PEF and irreversible electroporation (IRE). PEF is an ablation modality that does not rely on thermal processes to kill cells, and rather provides a means to destroy tissue without damaging the extracellular matrix while also potentially promoting an immune response. The PEF system used utilizes an advanced waveform design compared to IRE, is deliverable through a single needle and generates less mechanical trauma than IRE waveforms.
The results will be discussed during the presentation of “Advanced Biphasic Pulsed Electric Field (PEF) Stimulates a More Favorable Immune Response Profile versus Irreversible Electroporation (IRE) upon Ablation of Murine Breast Cancer,” on Wednesday, March 27 at 3:45 p.m. MT.
According to lead author Ebtesam Nafie, PhD, the research involved treating orthotopic breast cancer tumors in mice with either PEF, IRE or a sham procedure. They examined differences in treated and untreated contralateral tumor responses, post-ablation cytokine profiles in the tumor and circulating as well as intratumoral immune cell populations.
In the study, female BALB/c mice were orthotopically inoculated in the mammary fat pad with cells from the EMT6 murine breast cancer cell line. When the tumors reached 5–7 mm in size (10 days), the mice were randomly assigned to sham treatment, IRE or PEF, where the ablation technologies were titrated to target matched-size ablations for approximately 80% of the tumor volume.
PEF-treated tumor and serum cytokine levels were significantly different from the IRE and sham groups, indicating a different immunostimulatory profile, researchers said. Furthermore, flow cytometric analyses revealed increased percentages of key immune cells, including T-cells, B-cells, dendritic cells and natural killer cells in PEF-ablated tumors relative to IRE-ablated tumors. In addition, immunosuppressive cells such as mMDSC and M2 macrophages tended to be lower for PEF-ablated versus IRE-ablated tumors. This indicated a less inhibited immune environment.
“Our findings revealed a notable enhancement in tumor resolution not only within the ablated area but also in contralateral unablated tumors. This phenomenon serves as a compelling surrogate for what is commonly known as an ‘abscopal effect,’ suggesting promising avenues for advancing our understanding in cancer treatment,” said Dr. Nafie.
The findings of this study suggest that PEF technology may offer stronger immunostimulatory effects that result in improved local and distant tumor responses in a clinical setting, Dr. Nafie said. By comparing the results from this ablation technique to another form of ablation, these data suggest that clinicians may anticipate a higher rate of systemic tumor responses than what has previously been demonstrated for other ablation techniques.
Going forward, Dr. Nafie said they would like to further explore the specific differences in cell death mechanisms, post-ablative tumor microenvironment and other ablation delivery characteristics that may help explain the differentiated immune stimulation responses they observed in their initial study. Furthermore, they would also like to explore whether the increased local and systemic immune cell populations can be replicated in a clinical setting.
Dr. Nafie said this would involve, “investigating the immune potential of this form of PEF ablation in the clinic, such as checking various biomarkers for signs of immunostimulation, and ultimately determining whether off-target abscopal effects can be produced at a higher rate from advanced biphasic PEF form of ablation than what is generally recognized in the literature for other forms of ablation.”
