ENHANCING CHECKPOINT INHIBITOR THERAPY WITH ULTRASOUND STIMULATED MICROBUBBLES

Checkpoint inhibitor (CI) immunotherapy is playing an increasingly prominent role in the treatment of cancer but is effective and durable in only a subset of patients. There are concerted efforts to improve CI therapy through the use of multiple CIs or use of CIs in combination with other anti-cancer agents. Here we investigate the use of anti-vascular ultrasound-stimulated microbubble (USMB) treatments in combination with anti-PD-1 CI therapy. The colorectal cancer cell line CT26 was used to conduct longitudinal growth studies along with acute experiments to assess ultrasound-induced anti-tumor immune responses using flow cytometry and enzyme-linked immunospot (ELISPOT) analysis. Longitudinal experiments indicated that USMB + anti-PD-1 treatments significantly enhanced tumor growth inhibition and animal survival relative to monotherapies. Flow cytometry and ELISPOT data did not clearly support a T cell-dependent mechanism for the enhancement. Therefore, the results indicate the ability of anti-vascular USMBs to increase the anti-tumor effects of CI therapy; the specific mechanisms of enhancement remain to be established. (E-mail: goertz@sri.utoronto) (C) 2018 Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.