PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis
Tumor immunotherapy significantly rewards antigen-specific T-cell responses, which have been recognized as the foundation of adaptive immune responses. However, due to the immunosuppressive effects of the tumor microenvironment, it is still hard to activate T cells in situ. Especially, antigen-speci...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Extracellular Vesicle |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773041722000075 |
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| author | Xinyue Dai Zhaoshuo Wang Miao Fan Huifang Liu Xinjian Yang Xueyi Wang Xiaohan Zhou Yunlu Dai Jinchao Zhang Zhenhua Li |
| author_facet | Xinyue Dai Zhaoshuo Wang Miao Fan Huifang Liu Xinjian Yang Xueyi Wang Xiaohan Zhou Yunlu Dai Jinchao Zhang Zhenhua Li |
| author_sort | Xinyue Dai |
| collection | DOAJ |
| description | Tumor immunotherapy significantly rewards antigen-specific T-cell responses, which have been recognized as the foundation of adaptive immune responses. However, due to the immunosuppressive effects of the tumor microenvironment, it is still hard to activate T cells in situ. Especially, antigen-specific T cell activity is further limited as tumor cells can evade T cell attack via PD-1/PD-L1 axis. During this work, we used a dendritic cells (DCs)-derivate exosome vaccine to build an immunotherapeutic system that can simultaneously mediate antigenic T cell activity by carrying T cells activating CD80 and MHC to induce humoral immunity. More importantly, in order to interrupt tumor immune escape, we also engineered anti-PD-L1 antibodies (aPD-L1) to block PD-1/PD-L1 axis at the same time. Our antigens-feeding DCs-exosomes with aPD-L1 engineering represents a promising strategy for enhanced cancer immunotherapy by robust activating T cells. The outcomes demonstrated that Exo-OVA-aPD-L1 was successful in inhibiting the growth, recurrence, and metastasis of melanoma. |
| format | Article |
| id | doaj-art-cfc260a65e754c0888c89d0d5ea4d4fe |
| institution | Kabale University |
| issn | 2773-0417 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Extracellular Vesicle |
| spelling | doaj-art-cfc260a65e754c0888c89d0d5ea4d4fe2024-11-23T06:34:49ZengElsevierExtracellular Vesicle2773-04172022-12-011100012PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axisXinyue Dai0Zhaoshuo Wang1Miao Fan2Huifang Liu3Xinjian Yang4Xueyi Wang5Xiaohan Zhou6Yunlu Dai7Jinchao Zhang8Zhenhua Li9College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, ChinaCollege of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, ChinaCollege of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, ChinaCollege of Pharmaceutical Science, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, ChinaCollege of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, ChinaAffiliated Dongguan Hospital, Southern Medical University, Dongguan 523059, ChinaAffiliated Dongguan Hospital, Southern Medical University, Dongguan 523059, ChinaCancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, ChinaCollege of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, China; Corresponding author.Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523059, China; Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Guangdong 510515, China; Corresponding author at: Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523059, China.Tumor immunotherapy significantly rewards antigen-specific T-cell responses, which have been recognized as the foundation of adaptive immune responses. However, due to the immunosuppressive effects of the tumor microenvironment, it is still hard to activate T cells in situ. Especially, antigen-specific T cell activity is further limited as tumor cells can evade T cell attack via PD-1/PD-L1 axis. During this work, we used a dendritic cells (DCs)-derivate exosome vaccine to build an immunotherapeutic system that can simultaneously mediate antigenic T cell activity by carrying T cells activating CD80 and MHC to induce humoral immunity. More importantly, in order to interrupt tumor immune escape, we also engineered anti-PD-L1 antibodies (aPD-L1) to block PD-1/PD-L1 axis at the same time. Our antigens-feeding DCs-exosomes with aPD-L1 engineering represents a promising strategy for enhanced cancer immunotherapy by robust activating T cells. The outcomes demonstrated that Exo-OVA-aPD-L1 was successful in inhibiting the growth, recurrence, and metastasis of melanoma.http://www.sciencedirect.com/science/article/pii/S2773041722000075ExosomesCancer vaccinesAntigen-specific T-cell immune responsesPD-1/PD-L1 |
| spellingShingle | Xinyue Dai Zhaoshuo Wang Miao Fan Huifang Liu Xinjian Yang Xueyi Wang Xiaohan Zhou Yunlu Dai Jinchao Zhang Zhenhua Li PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis Extracellular Vesicle Exosomes Cancer vaccines Antigen-specific T-cell immune responses PD-1/PD-L1 |
| title | PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis |
| title_full | PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis |
| title_fullStr | PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis |
| title_full_unstemmed | PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis |
| title_short | PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis |
| title_sort | pd l1 antibodies armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating t cells and blocking pd 1 pd l1 axis |
| topic | Exosomes Cancer vaccines Antigen-specific T-cell immune responses PD-1/PD-L1 |
| url | http://www.sciencedirect.com/science/article/pii/S2773041722000075 |
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