Converting Immune Cold into Hot by Biosynthetic Functional Vesicles to Boost Systematic Antitumor Immunity

Ming Wu; Dongye Zheng; Da Zhang; Peiwen Yu; Lianli Peng; Feng Chen; Ziguo Lin; Zhixiong Cai; Jiong Li; Zuwu Wei; Xinyi Lin; Jingfeng Liu; Xiaolong Liu

doi:10.1016/j.isci.2020.101341

Converting Immune Cold into Hot by Biosynthetic Functional Vesicles to Boost Systematic Antitumor Immunity

iScience. 2020 Jul 24;23(7):101341. doi: 10.1016/j.isci.2020.101341. Epub 2020 Jul 6.

Authors

Ming Wu¹, Dongye Zheng², Da Zhang³, Peiwen Yu³, Lianli Peng⁴, Feng Chen², Ziguo Lin⁵, Zhixiong Cai³, Jiong Li⁵, Zuwu Wei³, Xinyi Lin³, Jingfeng Liu⁶, Xiaolong Liu⁷

Affiliations

¹ The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China; CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou 350116, P. R. China.
² The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China; CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, P. R. China.
³ The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou 350116, P. R. China.
⁴ College of Engineering and Computer Science, The Australian National University, Canberra 2601, Australia.
⁵ The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China.
⁶ The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China; CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou 350116, P. R. China; Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361024, P. R. China. Electronic address: drjingfeng@126.com.
⁷ The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China; CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou 350116, P. R. China; Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361024, P. R. China. Electronic address: xiaoloong.liu@gmail.com.

Abstract

Immune cold tumor characterized by low immunogenicity, insufficient and exhausted tumor-infiltrating lymphocytes, and immunosuppressive microenvironment is the main bottleneck responsible for low patient response rate of immune checkpoint blockade. Here, we developed biosynthetic functional vesicles (BFVs) to convert immune cold into hot through overcoming hypoxia, inducing immunogenic cell death, and immune checkpoint inhibition. The BFVs present PD1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the surface, whereas load catalase into their inner core. The TRAIL can specifically induce immunogenic death of cancer cells to initiate immune response, which is further synergistically strengthened by blocking PD1/PDL1 checkpoint signal through ectogenic PD1 proteins on BFVs. The catalase can produce O₂ to overcome tumor hypoxia, in turn to increase infiltration of effector T cells while deplete immunosuppressive cells in tumor. The BFVs elicit robust and systematic antitumor immunity, as demonstrated by significant regression of tumor growth, prevention of abscopal tumors, and excellent inhibition of lung metastasis.

Keywords: Cell Biology; Immune Response; Immunity.