A Combination of Radiotherapy, Hyperthermia, and Immunotherapy Inhibits Pancreatic Tumor Growth and Prolongs the Survival of Mice
Javed Mahmood, A. Alexander, Santanu Samanta, Shriya Kamlapurkar, Prerna Singh, Ali Saeed, France Carrier, Xuefang Cao, Hem D. Shukla, Željko Vujašković
Abstract
BACKGROUND: Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. Unfortunately, only 10-20% of PC patients are candidates for surgery, with the vast majority of patients with locally-advanced disease undergoing chemotherapy and/or radiation therapy (RT). Current treatments are clearly inadequate and novel strategies are crucially required. We investigated a novel tripartite treatment (combination of tumor targeted hyperthermia (HT), radiation therapy (RT), and immunotherapy (IT)) to alter immunosuppressive PC-tumor microenvironment (TME). (2). METHODS: In a syngeneic PC murine tumor model, HT was delivered before tumor-targeted RT, by a small animal radiation research platform (SARRP) followed by intraperitoneal injections of cytotoxic T-cell agonist antibody against OX40 (also known as CD134 or Tumor necrosis factor receptor superfamily member 4; TNFRSF4) that can promote T-effector cell activation and inhibit T-regulatory (T-reg) function. (3). RESULTS: < 0.01) in cytotoxic CD8 and CD4+ T-cells in the TME of the tripartite treatment groups. There was no tripartite-treatment-related toxicity observed in mice. (4). CONCLUSIONS: Tripartite treatment could be a novel therapeutic option for PC patients.