Hohyun Lee 1, Yutong Guo 1, James L Ross 2 3, Scott Schoen Jr 4, F Levent Degertekin 1, Costas Arvanitis 1 5
1G.W. School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
2Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
3Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
4Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
5Georgia Institute of Technology and Emory University, Department of Biomedical Engineering, Atlanta, GA, USA.
Corresponding author: Costas Arvanitis
Despite the challenges in treating glioblastomas (GBMs) with immune adjuvants, increasing evidence suggests that targeting the immune cells within the tumor microenvironment (TME) can lead to improved responses. Here, we present a closed-loop controlled, microbubble-enhanced focused ultrasound (MB-FUS) system and test its abilities to safely and effectively treat GBMs using immune checkpoint blockade. The proposed system can fine-tune the exposure settings to promote MB acoustic emission-dependent expression of the proinflammatory marker ICAM-1 and delivery of anti-PD1 in a mouse model of GBM. In addition to enhanced interaction of proinflammatory macrophages within the PD1-expressing TME and significant improvement in survival (P < 0.05), the combined treatment induced long-lived memory T cell formation within the brain that supported tumor rejection in rechallenge experiments. Collectively, our findings demonstrate the ability of MB-FUS to augment the therapeutic impact of immune checkpoint blockade in GBMs and reinforce the notion of spatially tumor-targeted (loco-regional) brain cancer immunotherapy.