| 论文题目: | TAT-mediated gp96 transduction to APCs enhances gp96-induced antiviral and antitumor T cell responses |
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| 作者: | Zhao Bao, Wang Yanzhong, Zhang Yu, Li Yang, Zhang Xiaojun, Xu Yaxing, Chen Lizhao, Li Changfei, Ju Ying, Meng Songdong |
| 联系作者: | Meng Songdong |
| 刊物名称: | Vaccine |
| 期: | 3 |
| 卷: | 31 |
| 页: | 545-552 |
| 年份: | 2013 |
| 影响因子: | 3.7 |
| 论文下载: | 下载地址 |
| 摘要: | The heat shock protein gp96 is an adjuvant that can elicit T cell responses against cancer and infectious diseases, via antigen presentation, in both rodent models and clinical trials. Its uptake and internalization into antigen presenting cells (APCs) is a critical step in gp96-mediated immune responses. This study examined strategies to improve the cell internalization and T cell activation of gp96. It was found that recombinant fusion with the cell-penetrating peptide TAT (trans-activator of transcription) slightly decreased the aggregation level of gp96 and significantly increased its internalization into macrophages. Furthermore, immunization with the TAT-gp96 fusion dramatically enhanced gp96-mediated hepatitis B virus (HBV)-specific T cell responses and its antiviral efficiency in HBV transgenic mice compared to rgp96. In addition, the inclusion of TAT significantly improved the antitumor T cell immune response to a gp96 vaccine in the B16 melanoma model. These results provide evidence that the efficient transduction of gp96 into APCs can significantly enhance the outcome of gp96-based immunotherapy, and therefore provide a basis for more efficient approaches to improving the immunoregulatory and adjuvant functions of this unique T cell adjuvant. (C) 2012 Elsevier Ltd. All rights reserved. |
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