期刊
INTERNATIONAL JOURNAL OF CANCER
卷 128, 期 3, 页码 702-714出版社
WILEY
DOI: 10.1002/ijc.25391
关键词
DNA vaccines; chemokines; IP-10; HPV-16 E7; CD4(+) Th1 T-cells; CD8(+) T-cells
类别
资金
- Korea Research Foundation (Korean Government
- MOEHRD) [KRF-2007-314-E00088]
- Korea Science and Engineering Foundation [R1-2006-000-10565-0]
- Ministry of Health and Welfare [070355]
- Ministry for Health, Welfare and Family Affairs, Republic of Korea [A062260]
DNA vaccines have emerged as an attractive approach to generate antigen-specific T-cell immune response. Nevertheless, the potency of DNA vaccines still needs to be improved for cancer immunotherapy. In this study, we explored whether functional linkage of a Th1-polarizing chemokine, IP-10, to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, enhanced DNA vaccine potency. IP-10 linkage changed the location of E7 from the nucleus to the endoplasmic reticulum and led to the secretion of functionally chemoattractive chimeric IP-10/E7 protein. In addition, this linkage drastically enhanced the endogenous processing of E7 antigen through MHC class I. More importantly, we found that C57BL/6 mice intradermally vaccinated with IP-10/E7 DNA exhibited a dramatic increase in the number of E7-specific CD4(+) Th1 T-cells and CD8(+) T-cells and, consequently, were strongly resistant over the long term to E7-expressing tumors compared to mice vaccinated with wild-type E7 DNA. Thus, because of the increase in tumor antigen-specific T-cell immune responses obtained through both enhanced antigen presentation and chemoattraction, vaccination with DNA encoding IP-10 linked to a tumor antigen holds great promise for treating tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据