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Tytuł:
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Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposomes for combination melanoma immunotherapy.
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Autorzy:
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Su Q; Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. , Tianjin 300192, China. .
Wang C; School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, Guanhai Road 346, Yantai 264003, China.
Song H; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China. .
Zhang C; Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China. .
Liu J; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China. .
Huang P; Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China. .
Zhang Y; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China. .
Zhang J; Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. .
Wang W; Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China. .
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Źródło:
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Journal of materials chemistry. B [J Mater Chem B] 2021 May 12; Vol. 9 (18), pp. 3892-3899.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Cambridge : Royal Society of Chemistry
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MeSH Terms:
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CpG Islands*
Epitopes/*immunology
Immunotherapy/*methods
Liposomes/*chemistry
Melanoma, Experimental/*therapy
Tryptophan/*analogs & derivatives
Animals ; Anions/chemistry ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/chemistry ; Cancer Vaccines/immunology ; Cations/chemistry ; Cell Line, Tumor ; Cell Survival/drug effects ; Dendritic Cells/cytology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Epitopes/chemistry ; Lipids/chemistry ; Liposomes/pharmacology ; Melanoma, Experimental/mortality ; Mice ; Mice, Inbred C57BL ; Nanostructures/chemistry ; Polymers/chemistry ; Survival Rate ; Tryptophan/chemistry
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Substance Nomenclature:
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0 (Anions)
0 (Cancer Vaccines)
0 (Cations)
0 (Epitopes)
0 (Lipids)
0 (Liposomes)
0 (Polymers)
8DUH1N11BX (Tryptophan)
XD0FY1J13B (1-methyltryptophan)
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Entry Date(s):
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Date Created: 20210430 Date Completed: 20210816 Latest Revision: 20210816
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Update Code:
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20240104
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DOI:
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10.1039/d1tb00256b
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PMID:
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33928989
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Immunotherapy is revolutionizing cancer treatment. Vaccination of antigenic peptides has been identified as a promising strategy for cancer immunotherapy while insufficient immune responses were stimulated due to low antigenicity. Moreover, immune checkpoint blockade therapy is still limited by a low objective response rate. In this work, cationic polymer-lipid hybrid nanovesicle (P/LNV)-based liposomes are designed to simultaneously deliver tumor vaccines composed of anionic antigen epitopes, toll-like receptor-9 agonist (TLR9), CpG (AE/CpG), and indoleamine-2,3-dioxygenase (IDO) inhibitor, 1-methyl-tryptophan (1-MT), to increase the immunogenicity of peptide antigens and meanwhile block the immune checkpoint. P/LNV liposomes efficiently enhanced the uptake of vaccines by dendritic cells (DCs) and improved the maturation of DCs indicated by the significantly increased percentage of CD86+MHCI+ DCs, resulting in a potent cytotoxic T-lymphocyte (CTL) response against B16-OVA tumor cells in vitro. Importantly, the combination immunotherapy showed significantly higher therapeutic efficiency towards melanoma tumors in mice, compared with an untreated or individual therapy modality. Mechanistically, the co-delivery system could elicit a strong cancer-specific T-cell response, as characterized by the remarkably increased infiltration of CD8+ T cells in the tumor and draining lymph nodes. Altogether, cationic liposomes delivered with tumor vaccines and IDO inhibitor provide a promising platform for cancer immunotherapy by provoking antitumor T-cell immunity and simultaneously reversing the immunosuppressive tumor microenvironment.
Erratum in: J Mater Chem B. 2021 Jun 3;9(21):4412. (PMID: 34013942)
