In vitro and ex vivo evaluation of a multi‐epitope heparinase vaccine for various malignancies

Cancer Science

Xu-Dong Tang¹  Shu-Liang Guo²  Guo-Zhen Wang¹  Ning Li¹  Yu-Yun Wu¹  Dian-Chun Fang¹  Ya-Han Fan¹ 

[1] Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China;Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China

关键词: Dendritic cells;    epitopes;    heparanase;    immunotherapy;    tumor antigens;   

DOI  :  10.1111/cas.12308

来源: Wiley

【 摘 要 】

Abstract

Previous studies have indicated that heparanase (Hpa) might represent a candidate universal tumor-associated antigen. However, vaccine therapy targeting only one cytotoxic T lymphocyte (CTL) epitope is suboptimal in preventing cancer. In the present study, we designed heparanase multi-epitope vaccines to increase the immune response to standard single heparanase epitopes. The results showed that multi-epitope vaccines Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 induced higher Hpa-specific lysis of various cancer cells from different tissues in a HLA-A2-restricted and heparanase-specific manner compared with the single epitope vaccines Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363, both in vitro and ex vivo. Heparanase multi-epitope vaccines not only induced the heparanase-specific CTL to lyse tumor cells but also increased CTL secretion of interferon-γ. However, these heparanase-specific CTL did not lyse heparanase-expressing autologous lymphocytes and dendritic cells, which confirms the safety of these multi-epitope vaccines. Therefore, the present study provides theoretical evidence for the use of heparanase multi-epitope vaccines for clinical application.

【 授权许可】

CC BY-NC-ND   
© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.