Stapled Liposomes Enhance Cross-Priming of Radio-Immunotherapy

The release of tumor-associated antigens (TAAs) and their cross-presentation in dendritic cells (DCs) are crucial for radio-immunotherapy. However, the irradiation resistance of tumor cells usually results in limited TAA generation and release. Importantly, TAAs internalized by DCs are easily degraded in lysosomes, resulting in unsatisfactory extent of TAA cross-presentation. Herein, an antigen-capturing stapled liposome (ACSL) with a robust structure and bioactive surface is developed. The ACSLs capture and transport TAAs from lysosomes to the cytoplasm in DCs, thereby enhancing TAA cross-presentation. l-arginine encapsulated in ACSLs induces robust T cell-dependent antitumor response and immune memory in 4T1 tumor-bearing mice after local irradiation, resulting in significant tumor suppression and an abscopal effect. Replacing l-arginine with radiosensitizers, photosensitizers, and photothermal agents may make ACSL a universal platform for the rapid development of various combinations of anticancer therapies.

Automated summary

The development of an antigen-capturing stapled liposome (ACSL) enhances the cross-presentation of tumor-associated antigens in dendritic cells, leading to a strong anti-tumor immune response. In mouse models, ACSL encapsulating l-arginine significantly suppresses tumor growth and induces an abscopal effect. This suggests that ACSL could be a universal platform for the rapid development of various combinations of anticancer therapies using radiosensitizers, photosensitizers, and photothermal agents.