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 (>=40Gy/s) favorably spares normal tissue from radiation-caused toxicity while maintaining anti-tumor effect 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 ultrahigh and CONV dose-rate irradiation to treat syngeneic subcutaneous pancreatic tumors generated in 8-10-week-old female C57BL6 mice. The efficacy of FLASH versus CONV radiotherapy (RT) at varying doses of 5, 8, 10, and 15Gy 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 from both FLASH and CONV RT compared to the control group. However, longer survival was observed for the FLASH group at 5Gy compared to CONV and control at either 5Gy, 10Gy, or 15Gy dose. Multiplex immunofluorescence and immunohistochemistry results showed higher T-cells 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.