Microshell Enhanced Acoustic Adjuvants for Immunotherapy in Glioblastoma

James Wang, Chin Hsin Huang, Oscar H. Echeagaray, Siamak Amirfakhri, Sarah L. Blair, William C. Trogler, Andrew C. Kummel, Clark C. Chen

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article number1900066
JournalAdvanced Therapeutics
Volume2
Issue number10
DOIs
StatePublished - Oct 1 2019

Bibliographical note

Funding Information:
The authors acknowledge the T32 Training grant (5T32CA153915-08) from NCI of NIH and the U54 supplementary grant (5U54CA132379-08) from collaboration with SDSU. Support from Viewpoint Medical is also greatly appreciated. C.C.C. was supported by 1RO1NS097649-01, 9R44GM128223-02, the Doris Duke Charitable Foundation Clinical Scientist Development Award, the Sontag Foundation Distinguished Scientist Award, the Kimmel Scholar Award, and BWF 1006774.01.

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • glioblastoma
  • immunotherapy
  • nanoparticles
  • programmed cell death 1
  • ultrasound

Fingerprint

Dive into the research topics of 'Microshell Enhanced Acoustic Adjuvants for Immunotherapy in Glioblastoma'. Together they form a unique fingerprint.

Cite this