Evaluation of immune-modulating drugs for use in drug-eluting microsphere transarterial embolization

Cancer immunotherapy has yet to reach its full potential due in part to limited response rates and side effects inherent to systemic delivery of immune-modulating drugs. Local administration of immunotherapy using drug-eluting embolic (DEE) microspheres as drug delivery vehicles for direct infusion into tumor-feeding arteries might increase and prolong tumor drug concentrations and reduce systemic drug exposure, potentially improving the risk-to-benefit ratio of these agents. The purpose of this study was to evaluate the ability of four immune modulators affecting two different immune pathways to potentiate replication of immune cells from a woodchuck model of hepatocellular carcinoma. DSR 6434, a Toll-like receptor agonist, and BMS-202, a PD-L1 checkpoint inhibitor, induced immune cell replication and were successfully loaded into radiopaque DEE microspheres in high concentrations. Release of DSR 6434 from the DEE microspheres was rapid (t_99% = 0.4 h) upon submersion in a physiologic saline solution while BMS-202 demonstrated a more sustained release profile (t_99% = 17.9 h). These findings demonstrate the feasibility of controlled delivery of immune-modulating drugs via a local DEE microsphere delivery paradigm.