TAT-mediated gp96 transduction to APCs enhances gp96-induced antiviral and antitumor T cell responses

详细信息    查看全文

• 作者：Bao Zhao^a ; ^b ; Yanzhong Wang^a ; Yu Zhang^a ; ^b ; Yang Li^a ; Xiaojun Zhang^a ; Yaxing Xu^a ; Lizhao Chen^a ; Changfei Li^a ; Ying Ju^a ; Songdong Meng^a ; ^{mengsd@im.ac.cn}
• 关键词：Gp96 ; TAT ; T cell response ; Internalization ; HBV
• 刊名：Vaccine
• 出版年：2013
• 出版时间：7 January, 2013
• 年：2013
• 卷：31
• 期：3
• 页码：545-552
• 全文大小：1223 K

文摘

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.