Journal
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 15, Issue 5, Pages 1018-1032Publisher
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2019.2755
Keywords
Immunotherapy; Dendritic Cell (DC)-Based Tumor Vaccines; Mannose; Polydeoxynucleotides; Liposome
Funding
- Programs for Chang jiang Scholars and Innovative Research Team in University [IRT_15R13]
- National Natural Scientific Foundation of China [81430055, 81372452]
- International Cooperation Project of the Ministry of Science and Technology of China [2015DFA31320]
- Project for Innovative Research Team in Guangxi Natural Science Foundation [2015GXNSFFA139001]
- Project of Science and Technology of Guangxi [14125008-2-12, 1599005-2-10]
- Project for International Nanobody Research Center of Guangxi [GuiKe-AD17195001]
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Dendritic cell (DC)-based tumor vaccines are a promising immunotherapeutic method of cancer treatment. However, their therapeutic applications are significantly limited by their weak immunogenicity, costly culturing steps, and easily degradable properties. Thus, the anti-tumor activity for the vaccines should be improved. In this study, a novel lipid nanoparticle (M/CpG-ODN-H22-Lipo) was developed, which was conjugated with synthetic CpG oligodeoxynucleotides (CpG-ODN) and mannose and then loaded with H22 hepatoma lysate. Our data corroborate that M/CpG-ODN-H22-Lipo selectively targeted DCs and significantly increased their induced-maturation. Besides, the vaccine halted tumor growth and extended survival of mice with hepatocellular carcinoma. Moreover, M/CpG-ODN-H22-Lipo treatment reduced the percentages of myeloid-derived suppressor cells (in the tumor and bone marrow) and regulatory T cells (Treg) in the spleen. In contrast, the number of IFN-gamma-positive cells in the spleen along with the serum IgG levels were up-regulated. Moreover, tumor angiogenesis and tumor-cell proliferation were halted by the treatment of M/CpG-ODN-H22-Lipo, whereas tumor cell apoptosis was up-regulated. Our data revealed that CD8(+) T cells and NK cells were vital to mediate the anti-tumor immunity of M/CpG-ODN-H22-Lipo treatment. In sum, the results here proved M/CpG-ODN-H22-Lipo vaccine a safe, specific and effective DC-based anti-tumor immunotherapy with great potential for clinical applications.
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