未找到相关数据
Targeted siRNA Silencing of Indoleamine 2, 3-Dioxygenase in Antigen-presenting Cells Using Mannose- conjugated Liposomes: A Novel Strategy for Treatment of Melanoma
被引：29
|作者：
Chen, Di
[1
,2
,3
,4
,5
,6
,8
]
Koropatnick, James
[1
,2
,3
,4
,5
,6
,7
,8
]
Jiang, Nan
[1
,2
,3
,4
,5
,6
]
Zheng, Xiufen
[1
,2
,3
,4
,5
,6
,7
]
Zhang, Xusheng
[1
,2
,3
,4
,5
,6
]
Wang, Hongmei
[9
]
Yuan, Keng
[9
]
Siu, King Sun
[1
,2
,3
,4
,5
,6
,8
]
Shunnar, Aminah
[1
,2
,3
,4
,5
,6
]
Way, Colin
[1
,2
,3
,4
,5
,6
,8
]
Min, Wei-Ping
[1
,2
,3
,4
,5
,6
,7
,8
,9
]
机构：
[1] Western Univ, Dept Pathol, London, ON, Canada
[2] Western Univ, Dept Surg, London, ON, Canada
[3] Western Univ, Dept Oncol, London, ON, Canada
[4] Western Univ, Dept Microbiol & Immunol, London, ON, Canada
[5] Western Univ, Dept Physiol, London, ON, Canada
[6] Western Univ, Dept Pharmacol, London, ON, Canada
[7] Lawson Hlth Res Inst, London, ON, Canada
[8] London Reg Canc Program, London, ON, Canada
[9] Nanchang Univ, Inst Immunomodulat & Immunotherapy, Jiangxi Acad Med Sci, Nanchang, Peoples R China
关键词：
IDO;
mannose;
liposome;
siRNA;
antigen-presenting cells;
PLASMACYTOID DENDRITIC CELLS;
T-CELL;
RECEPTOR;
2,3-DIOXYGENASE;
INHIBITION;
PROLIFERATION;
THERAPEUTICS;
INDUCTION;
DELIVERY;
DISEASE;
D O I：
10.1097/CJI.0000000000000022
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Indoleamine 2, 3-dioxygenase (IDO) expression in dendritic cells (DCs) leads to the inhibition of T-cell activation, induction of T-cell apoptosis, and promotion of T-cell differentiation into regulatory T cells. All of these could promote tumor escapement of the host's immune surveillance system. We hypothesized that DC-targeted gene silencing of IDO would enhance antitumor immunity and thus restrain tumor growth. Mannose receptors are highly expressed in antigen-presenting cells (APCs) including DCs. In this study, we developed a novel APC-targeted small interfering RNA delivery system using mannosed liposomes (Man-lipo) with encapsulated IDO small interfering RNA (Man-lipo-siIDO), which preferentially knocked down IDO expression in draining lymph node and spleen of melanoma-bearing mice. Mice treated with Man-lipo-siIDO displayed a delayed time of onset of implanted murine melanomas, increased survival time, reduced tumor size, and increased reactivity of T cells from spleen and lymph nodes against melanoma antigens. The enhanced antitumor immunity may be linked to inhibition of apoptosis in CD8(+) and CD4(+) T cells as well as Treg cells in spleen and lymph nodes. This study is the first to demonstrate that Man-lipo-siIDO can preferentially targets APCs and efficiently silence IDO expression in vitro and in vivo; events expected to enhance antitumor immune reactions against melanoma xenografts. This study supports the hypothesis that Man-lipo-siIDO may possess the potential for development as an immune-targeting therapeutic anticancer agent.
引用
收藏
页码：123 / 134
页数：12
相关论文