By harvesting nanovesicles derived from DCs that were transduced with recombinant adenovirus to induce expression of multiple antigen epitopes on MHC I, transmembrane-anchored anti-PD-1 scFv, and B7 costimulatory molecules simultaneously, Liu and Liu et al. created a nanovaccine that spatiotemporally combined various signals. The nanovaccine enriched in LNs upon s.c. injection into mice, elicited polyfunctional and antigen-specific CD8+ T cells, decreased the frequency of dysfunctional PD1+CD38+CD8+ T cells among TILs, led to complete tumor regression that was dependent on co-delivery of B7 and anti-PD-1, and induced immunological memory.
Contributed by Ute Burkhardt
ABSTRACT: The strategy of combining a vaccine with immune checkpoint inhibitors has been widely investigated in cancer management, but the complete response rate for this strategy is still unresolved. We describe a genetically engineered cell membrane nanovesicle that integrates antigen self-presentation and immunosuppression reversal (ASPIRE) for cancer immunotherapy. The ASPIRE nanovaccine is derived from recombinant adenovirus-infected dendritic cells in which specific peptide-major histocompatibility complex class I (pMHC-I), anti-PD1 antibody and B7 co-stimulatory molecules are simultaneously anchored by a programmed process. ASPIRE can markedly improve antigen delivery to lymphoid organs and generate broad-spectrum T-cell responses that eliminate established tumours. This work presents a powerful vaccine formula that can directly activate both native T cells and exhausted T cells, and suggests a general strategy for personalized cancer immunotherapy.
Author Info: (1) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular
Author Info: (1) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (2) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (3) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (4) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (5) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (6) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (7) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (8) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (9) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (10) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. (11) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China. (12) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China. (13) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China. (14) Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Clinical Imaging Research Centre, Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, Singapore. chen.shawn@nus.edu.sg. (15) State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. gangliu.cmitm@xmu.edu.cn. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China. gangliu.cmitm@xmu.edu.cn. MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China. gangliu.cmitm@xmu.edu.cn.
