Ultrasound-Activatable <i>In Situ</i> Vaccine for Enhanced Antigen Self- and Cross-Presentation to Overcome Cancer Immunotherapy Resistance.
basic_science · Level V
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- Record sourced from PubMed, PMID 39051505.
- Also identified by DOI 10.1021/acsnano.4c04045.
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Abstract
Insufficient antigen self-presentation of tumor cells and ineffective antigen cross-presentation by dendritic cells (DCs) contribute to diminished immune recognition and activation, which cause resistance to immunotherapies. Herein, we present an ultrasound-activatable <i>in situ</i> vaccine by utilizing a hybrid nanovesicle composed of a thylakoid (TK)/platelet (PLT) membrane and a liposome encapsulating DNA methyltransferase inhibitor zebularine (Zeb) and sonosensitizer hematoporphyrin monomethyl ether (HMME). Upon local exposure to ultrasound, reactive oxygen species (ROS) are generated and induce the sequential release of the payloads. Zeb can efficiently inhibit tumor DNA hypermethylation, promoting major histocompatibility complex class I (MHC-I) molecules-mediated antigen self-presentation to improve immune recognition. Meanwhile, the catalase on the TK membrane can decompose the tumoral overexpressed H<sub>2</sub>O<sub>2</sub> into O<sub>2</sub>, which boosts the generation of ROS and the destruction of tumor cells, resulting in the <i>in situ</i> antigen release and cross-presentation of tumor antigens by DCs. This <i>in situ</i> vaccine simultaneously promotes antigen self-presentation and cross-presentation, resulting in heightened antitumor immunity to overcome resistance.