A research team has developed a combination immunotherapy that uses an electrical ablation technique to enhance the efficacy of immune cell therapy against liver cancer.

The team, led by Professor Wooram Park of the Department of Integrative Biotechnology at Sungkyunkwan University (SKKU), used irreversible electroporation (IRE) to reshape the immunosuppressive tumor microenvironment in liver cancer and enhance the anticancer activity of chimeric antigen receptor natural killer (CAR-NK) cells. The team also identified the key molecular mechanisms underlying this therapeutic effect. Joo Dong Park and Ha Eun Shin, researchers in Professor Park’s group, served as co-first authors of the study.

Conventional immune cell-based cancer therapies often suffer from limited infiltration of therapeutic cells into tumors and reduced efficacy due to the immunosuppressive tumor microenvironment. Hepatocellular carcinoma, in particular, has a highly immunosuppressive environment, making it difficult to achieve sufficient therapeutic effects with CAR-NK cell therapy alone.

To overcome this limitation, the research team developed an approach using IRE, a clinically approved nonthermal ablation technique, as a means of remodeling the tumor microenvironment.

IRE destroys tumor cells using high-voltage pulsed electric fields. This process induces the release of damage-associated molecular patterns (DAMPs) and chemokines—chemical signaling proteins that attract immune cells—thereby transforming the tumor microenvironment into one that is more favorable for NK cell activity.

The researchers found that chemokine levels within tumors increased significantly after IRE treatment, leading to the early recruitment of NK cells. They also identified a mechanism in which increased reactive oxygen species (ROS) generated by IRE made residual tumor cells markedly more susceptible to NK cell-mediated killing.

The team then combined IRE with glypican-3 (GPC3)-targeted CAR-NK cells generated using lipid nanoparticle (LNP)-based gene delivery technology. The combination produced substantially stronger tumor control than either treatment alone.

In vitro, IRE-treated liver cancer cells were rapidly eliminated by CAR-NK cells. Across multiple preclinical models, the combination of IRE and CAR-NK cell therapy also demonstrated superior tumor suppression and prolonged survival.

Professor Wooram Park said, “This study is significant because it combines IRE, an LNP platform, and CAR-NK cells—all technologies that have already entered or are approaching clinical application—to improve the local tumor environment and deliver precision cellular immunotherapy. We expect this approach to develop into a combination therapy that can be translated more rapidly into clinical practice.”

The findings were published online in March 2026 in Signal Transduction and Targeted Therapy(impact factor 81.2), one of the leading international journals in biochemistry and molecular biology, ranked in the top 0.2% of its field.