Leveraging the Immune Response from LIFE Biomaterial and Photon-Flash in Pre-Clinical Pancreatic Cancer Treatment

Pre-clinical animal studies evaluating the 'flash effect' caused by ultra-high dose rate (≥40 Gy/s) favorably spares normal tissue from radiation-caused toxicity while maintaining anti-tumor effects like conventional (CONV) radiation. The goal of this study is to leverage an immune response resulting from the treatment combination of flash radiotherapy (Flash-RT) and LIFE (liquid immunogenic fiducial eluter) biomaterial incorporating an anti-mouse CD40 monoclonal antibody to enhance the therapeutic ratio in pancreatic cancer. Methods: A small animal FLASH radiation research platform (FLASH-SARRP) was utilized to deliver both ultra-high and CONV dose-rate irradiation to treat syngeneic subcutaneous pancreatic tumors generated in 8-10-week-old male and female C57BL6 mice. The efficacy of FLASH versus CONV radiotherapy (RT) at varying doses of 5, 8, 10, and 15 Gy delivered in a single fraction was evaluated by assessing tumor growth and mice survival over time or comparing tumor weight at 10 days post-treatment. Results: Similar tumor control capability was observed by the high-dose rate and conventional RT related to the control group. Nevertheless, longer survival was observed for the FLASH group at 5 Gy compared to CONV and control at either 5 Gy, 10 Gy, or 15 Gy doses. Multiplex immunofluorescence and immunohistochemistry results showed higher T-cell infiltration within the combination of RT (either FLASH or CONV) and LIFE biomaterial-treated tumors compared to the control cohort. Conclusions: This animal study serves as an impetus for future studies leveraging the immune response using the combination of FLASH and LIFE Biomaterial to enhance the efficacy of pancreatic cancer treatment.