Microshell Enhanced Acoustic Adjuvants for Immunotherapy in Glioblastoma

Abstract A key challenge in immunotherapy for glioblastomas, the most common form of primary adult brain cancer, involves the paucity of immune‐stimulatory cells in its “cold” immune‐microenvironment. Herein, mechanical acoustic ablation focused by perfluorocarbon (PFC) liquid filled silica microshells is applied to induce immunogenicity via in situ ultrasonic lysis. The inert PFC filled ultra‐thin walled silica microshells promote mechanical ablation while aiding in ultrasound guidance. In the presence of programmed cell death protein 1 (PD‐1) blockade, tumor injury sites exhibit an increase in tumor infiltrating lymphocytes and interferon‐γ (IFN‐γ) by 1–2 orders of magnitude. At least 75% of mice grafted with the advanced murine glioblastoma tumors achieve remission when treated with a combination of microshell enhanced ablation and PD‐1 blockade, which indicates a synergistic effect. In contrast, none of the mice treated with single therapies achieve durable remission. Likelihood of remission correlated with the abundance of tumor infiltrating lymphocytes ( p < 0.001) and IFN‐γ levels ( p = 0.001). This study demonstrates a PFC filled ultrathin walled microshell enhanced ablation strategy that induces a “hot” immune‐microenvironment and augments efficacy of immune checkpoint blockade against advanced tumors.