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An indoleamine 2, 3-dioxygenase siRNA nanoparticle-coated and Trp2-displayed recombinant yeast vaccine inhibits melanoma tumor growth in mice
Liu, Dong-qun1,2; Lu, Shuai1; Zhang, Ling-xiao1,2; Ji, Mei1,2; Liu, Shu-ying1; Wang, Shao-wei1; Liu, Rui-tian1
2018-03-10
发表期刊JOURNAL OF CONTROLLED RELEASE
ISSN0168-3659
卷号273页码:1-12
摘要Therapeutic vaccine is a promising approach in cancer therapy. But tumor-associated antigen peptides have weak immunogenicity and cancer patients are often characterized by immunosuppression and tolerance, leading to less efficiency of immunotherapy. We here successfully developed indoleamine 2, 3-dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2 (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP). YCPs had positive charges with a diameter of approximately 5 mu m, resulting in selective phagocytosis by APC cells. YCP-delivered siRNA and Trp2 successfully escaped from phagosomes, efficiently inhibited IDO expression in DCs, promoted the immune reaction of T cell against Trp2, increased the secretion of proin-flammatory cytokines such as IFN-gamma, TNF-alpha, and IL-6, and decreased the generation of regulatory T cells. Moreover, YCPs significantly inhibited melanoma tumor growth by alleviating immune tolerance and promoting Trp2-specific CD8(+) T cell immune response. These results suggest that Saccharomyces cerevisiae as a combined immunotherapeutic platform to simultaneously delivery IDO-siRNA and Trp2 epitope peptide is a promising vaccine system for melanoma treatment.
关键词Small Interfering Rna (siRna) Indoleamine 2 Nanoparticle 3-dioxygenase (Ido) Tyrosinase-related Protein 2 (Trp2) Saccharomyces Cerevisiae Melanoma Tumor
文章类型Article
WOS标题词Science & Technology ; Physical Sciences ; Life Sciences & Biomedicine
DOI10.1016/j.jconrel.2018.01.013
收录类别SCI
语种英语
关键词[WOS]DENDRITIC CELL MATURATION ; SACCHAROMYCES-CEREVISIAE ; CANCER-IMMUNOTHERAPY ; TRYPTOPHAN CATABOLISM ; CROSS-PRESENTATION ; DNA COMPLEXES ; DELIVERY ; 2,3-DIOXYGENASE ; ANTIGEN ; TOLERANCE
WOS研究方向Chemistry ; Pharmacology & Pharmacy
WOS类目Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
项目资助者National Natural Science Foundation of China(81371208 ; National Science and Technology Major Projects of New Drugs(2014ZX09102045-005 ; State Key Laboratory of Biochemical Engineering(2015KF-02) ; 81402837 ; 2014ZX09102041-007) ; 31401158)
WOS记录号WOS:000426298100001
引用统计
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/24035
专题生化工程国家重点实验室
作者单位1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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Liu, Dong-qun,Lu, Shuai,Zhang, Ling-xiao,et al. An indoleamine 2, 3-dioxygenase siRNA nanoparticle-coated and Trp2-displayed recombinant yeast vaccine inhibits melanoma tumor growth in mice[J]. JOURNAL OF CONTROLLED RELEASE,2018,273:1-12.
APA Liu, Dong-qun.,Lu, Shuai.,Zhang, Ling-xiao.,Ji, Mei.,Liu, Shu-ying.,...&Liu, Rui-tian.(2018).An indoleamine 2, 3-dioxygenase siRNA nanoparticle-coated and Trp2-displayed recombinant yeast vaccine inhibits melanoma tumor growth in mice.JOURNAL OF CONTROLLED RELEASE,273,1-12.
MLA Liu, Dong-qun,et al."An indoleamine 2, 3-dioxygenase siRNA nanoparticle-coated and Trp2-displayed recombinant yeast vaccine inhibits melanoma tumor growth in mice".JOURNAL OF CONTROLLED RELEASE 273(2018):1-12.
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