These authors contributed equally to this study.
In vitro and ex vivo evaluation of a multi-epitope heparinase vaccine for various malignancies
Article first published online: 29 NOV 2013
© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the 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.
Volume 105, Issue 1, pages 9–17, January 2014
How to Cite
Cancer Sci 105 (2014) 9–17
- Issue published online: 24 JAN 2014
- Article first published online: 29 NOV 2013
- Accepted manuscript online: 24 OCT 2013 01:12AM EST
- Manuscript Accepted: 18 OCT 2013
- Manuscript Revised: 15 OCT 2013
- Manuscript Received: 31 JUL 2013
- National Nature Science Foundation of China. Grant Numbers: 30800520, 81372470
- Key Project of Science and Technology of Chongqing. Grant Number: 2008AB5002
- Chongqing Science Fund for Distinguished Young Scholars. Grant Number: 2009BA5045
- Dendritic cells;
- tumor antigens
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.