Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity

被引:205
作者
Hamdy, Samar [1 ]
Molavi, Ommoleila [1 ]
Ma, Zengshuan [1 ]
Haddadi, Azita [1 ]
Alshamsan, Aws [1 ]
Gobti, Zahra [1 ]
Elhasi, Sara [1 ]
Samuel, John [1 ]
Lavasanifar, Afsaneh [1 ]
机构
[1] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada
关键词
PLGA; lipid A and melanoma;
D O I
10.1016/j.vaccine.2008.07.035
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The purpose of this study was to evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA)-based vaccines in breaking immunotolerance to cancer-associated self-antigens. Vaccination of mice bearing melanoma B16 tumors with PLGA nanoparticles (NP) co-encapsulating the poorly immunogenic melanoma antigen, tyrosinase-related protein 2 (TRP2), along with Toll-like receptor (TLR) ligand (7-acyl lipid A) was examined. Remarkably, this vaccine was able to induce therapeutic anti-tumor effect. Activated TRP2-specific CD8 T cells were capable of interferon (IFN)-gamma secretion at lymph nodes and spleens of the vaccinated mice. More importantly, TRP2/7-acyl lipid A-NP treated group has shown immunostimulatory mileu at the tumor microenvironment, as evidenced by increased level of pro-inflammatory cytokines compared to control group. These results support the potential use of PLGA nanoparticles as competent carriers for future cancer vaccine formulations. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5046 / 5057
页数:12
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