In vitro and ex vivo evaluation of a multi-epitope heparinase vaccine for various malignancies.
Bottom Line: 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.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.
Affiliation: 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.Show MeSH
Related in: MedlinePlus
Mentions: Heparanase is expressed in immunologically competent cells, natural killer cells and inflammatory cells such as neutrophils, granulocytes and activated T and B cells.25 Theoretically, immunotherapy targeting heparanase might have side-effects on the immune system. To investigate the effect of heparanase-specific CTL on immunologically activated lymphocytes, CTL induced by heparanase-specific peptides were also used to lyse autologous lymphocytes and DC. The results indicate that multi-epitope vaccines and their corresponding single peptides from heparanase did not lyse autologous lymphocytes or DC in vitro or ex vivo (Fig.5).
Affiliation: 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.