Journal
CANCER SCIENCE
Volume 105, Issue 1, Pages 9-17Publisher
WILEY
DOI: 10.1111/cas.12308
Keywords
Dendritic cells; epitopes; heparanase; immunotherapy; tumor antigens
Categories
Funding
- National Nature Science Foundation of China [30800520, 81372470]
- Key Project of Science and Technology of Chongqing (CSTC) [2008AB5002]
- Chongqing Science Fund for Distinguished Young Scholars (CSTC) [2009BA5045]
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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-. 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.
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