Proton-driven transformable nanovaccine for cancer immunotherapy

• Published in: Nature nanotechnology Vol. 15; no. 12; pp. 1053 - 1064
• Main Authors: Gong, Ningqiang, Zhang, Yuxuan, Teng, Xucong, Wang, Yongchao, Huo, Shuaidong, Qing, Guangchao, Ni, Qiankun, Li, Xianlei, Wang, Jinjin, Ye, Xiaoxia, Zhang, Tingbin, Chen, Shizhu, Wang, Yongji, Yu, Jie, Wang, Paul C, Gan, Yaling, Zhang, Jinchao, Mitchell, Michael J, Li, Jinghong, Liang, Xing-Jie
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2020
• Subjects: Animal models; Animals; Antibodies; Antigens; Antigens - administration & dosage; Antigens - therapeutic use; Cancer; Cancer immunotherapy; Cancer vaccines; Cancer Vaccines - administration & dosage; Cancer Vaccines - therapeutic use; Cell Line, Tumor; Cytoplasm; Delayed-Action Preparations - chemistry; Female; Human papillomavirus; Humans; Hydrogen-Ion Concentration; Immune response; Immune response (cell-mediated); Immune system; Immunogenicity; Immunotherapy; Inflammasomes; Mice; Mice, Inbred C57BL; Nanospheres; Nanospheres - chemistry; Nanostructure; Neoplasms - pathology; Neoplasms - prevention & control; PD-L1 protein; Peptides; Polymers; Polymers - chemistry; Protons; Regression models; Survival; Toxicity; Tumors; Vaccines; Viruses
• ISSN: 1748-3387; 1748-3395
• DOI: 10.1038/s41565-020-00782-3

Cancer vaccines hold great promise for improved cancer treatment. However, endosomal trapping and low immunogenicity of tumour antigens usually limit the efficiency of vaccination strategies. Here, we present a proton-driven nanotransformer-based vaccine, comprising a polymer-peptide conjugate-based nanotransformer and loaded antigenic peptide. The nanotransformer-based vaccine induces a strong immune response without substantial systemic toxicity. In the acidic endosomal environment, the nanotransformer-based vaccine undergoes a dramatic morphological change from nanospheres (about 100 nanometres in diameter) into nanosheets (several micrometres in length or width), which mechanically disrupts the endosomal membrane and directly delivers the antigenic peptide into the cytoplasm. The re-assembled nanosheets also boost tumour immunity via activation of specific inflammation pathways. The nanotransformer-based vaccine effectively inhibits tumour growth in the B16F10-OVA and human papilloma virus-E6/E7 tumour models in mice. Moreover, combining the nanotransformer-based vaccine with anti-PD-L1 antibodies results in over 83 days of survival and in about half of the mice produces complete tumour regression in the B16F10 model. This proton-driven transformable nanovaccine offers a robust and safe strategy for cancer immunotherapy.