期刊
JOURNAL OF IMMUNOTHERAPY
卷 40, 期 2, 页码 62-70出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0000000000000156
关键词
human papillomavirus; DNA vaccine; E6 and E7 oncogenes; tumor; immune checkpoint blockade; PD-L1
We have previously shown that a novel DNA vaccine technology of codon optimization and the addition of ubiquitin sequences enhanced immunogenicity of a herpes simplex virus 2 polynucleotide vaccine in mice, and induced cell-mediated immunity when administered in humans at relatively low doses of naked DNA. We here show that a new polynucleotide vaccine using the same technology and encoding a fusion protein of the E6 and E7 oncogenes of high-risk human papillomavirus type 16 (HPV16) is immunogenic in mice. This vaccine induces long-lasting humoral and cell-mediated immunity and protects mice from establishment of HPV16-E7-expressing tumors. In addition, it suppresses growth of readily established tumors and shows enhanced efficacy when combined with immune checkpoint blockade targeted at PD-L1. This vaccine also facilitates rejection of HPV16-E7-expressing skin grafts that demonstrate epidermal hyperplasia with characteristics of cervical and vulvar intra-epithelial neoplasia. Clinical studies evaluating the efficacy of this vaccine in patients with HPV16(+) premalignancies are planned.
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