The University of Texas MD Anderson Cancer Center researchers have developed the Microbubble-assisted UltraSound-guided Immunotherapy of Cancer (MUSIC) platform for improving antitumour immune and checkpoint inhibitor responses.
The new ultrasound-guided cancer immunotherapy platform generates systemic antitumor immunity and improves the therapeutic efficacy of immune checkpoint blockade.
Employing nanocomplexes combined with microbubbles, it provides cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an immunotransmitter involved in anticancer immunity, into antigen-presenting cells (APCs).
The microbubbles release cGAMP inside the APCs to activate the GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and help stimulate type I interferon responses, which are important for priming tumour-specific T cells.
When given as monotherapy in breast cancer models, the MUSIC approach showed 60% of complete tumour eradication rate in the preclinical study.
The platform also significantly improved antitumor responses when it was combined with an anti-PD-1 antibody.
Minimal toxicity effects, such as decreased systemic disease progression and enhanced primary tumour control, were observed.
Furthermore, the combination therapy showed a 76% increase in median survival compared to either therapy alone.
The University of Texas MD Anderson Cancer Center Radiation Oncology assistant professor Wen Jiang said: “By investigating the mechanisms of action in producing a robust STING activation, we identified a new strategy to activate both the innate and adaptive antitumor immune responses.”
“Our findings show that the MUSIC strategy is capable of paving the way toward novel image-guided strategies for targeted cancer immunotherapy.
“Our MUSIC platform is exciting because it provides a new framework for developing image-guided immunotherapy by using acoustically responsive biomaterials to enable efficient, targeted and robust immune activation to produce potent antitumor effects while minimising systemic toxicity.”
The National Cancer Institute, the Cancer Prevention and Research Institute of Texas (CPRIT), and the Department of Defense provided funds for the study.