Targeted Immunomodulation in PDAC by Combining Proton Radiation and H-FIRE
Pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer, is one of the deadliest cancers and remains largely resistant to immunotherapy because dense tissue surrounding these tumors can block or suppress cancer-fighting immune cells. New strategies are urgently needed to make these tumors visible and vulnerable to the immune system. Our research tests a new combination approach designed to make these tumors immune responsive. This novel treatment strategy combines four components:
- High-frequency irreversible electroporation (H-FIRE), which uses short electrical pulses to kill tumor cells while releasing tumor-related signals that may help prime the immune system to recognize the cancer
- Proton radiation to increase stress inside cancer cells and further enhance immune activation
- A drug that blocks cancer cells from shutting down immune signaling
- Immunotherapy to stimulate T-cells so they can attack the cancer more effectively
Using animal models, we are studying how each treatment contributes to immune activation and identifying the most effective timing and dose with the aim to improve tumor control, survival and immune memory. Ultimately, this work may provide a framework for future clinical trials and expand treatment options for patients with pancreatic cancer.
