PMID- 21505182 OWN - NLM STAT- MEDLINE DCOM- 20120105 LR - 20201226 IS - 1940-6215 (Electronic) IS - 1940-6215 (Linking) VI - 4 IP - 8 DP - 2011 Aug TI - Multiple antigenic peptides of human heparanase elicit a much more potent immune response against tumors. PG - 1285-95 LID - 10.1158/1940-6207.CAPR-11-0083 [doi] AB - Peptide vaccination for cancer immunotherapy requires an ideal immune response induced by epitope peptides derived from tumor-associated antigens (TAA). Heparanase is broadly expressed in various advanced tumors. Accumulating evidence suggests that heparanase can serve as a universal TAA for tumor immunotherapy. However, due to the low immunogenicity of peptide vaccines, an ideal immune response against tumors usually cannot be elicited in patients. To increase the immunogenicity of peptide vaccines, we designed three 4-branched multiple antigenic peptides (MAP) on the basis of the human leukocyte antigen (HLA)-A2-restricted cytotoxic T lymphocyte (CTL) epitopes of human heparanase that we identified previously as antigen carriers. Our results show that MAP vaccines based on the HLA-A2-restricted CLT epitopes of human heparanase were capable of inducing HLA-A2-restricted and heparanase-specific CTL in vitro and in mice. Moreover, compared with their corresponding linear peptides, heparanase MAP vaccines elicited much stronger lysis of tumor cells by activating CD8(+) T lymphocytes and increasing the releasing of IFN-gamma. However, these heparanase-specific CTLs did not lyse heparanase-expressing autologous lymphocytes and dendritic cells, which confirm the safety of these MAP vaccines. Therefore, our findings indicate that MAP vaccines based on CTL epitopes of human heparanase can be used as potent immunogens for tumor immunotherapy because of advantages such as broad spectrum, high effectiveness, high specificity, and safety. FAU - Wang, Guo-Zhen AU - Wang GZ AD - Institute of Gastroenterology, Third Military Medical University, Chongqing 400038, China. FAU - Tang, Xu-Dong AU - Tang XD FAU - Lu, Mu-Han AU - Lu MH FAU - Gao, Jin-Hua AU - Gao JH FAU - Liang, Guang-Ping AU - Liang GP FAU - Li, Ning AU - Li N FAU - Li, Chang-Zhu AU - Li CZ FAU - Wu, Yu-Yun AU - Wu YY FAU - Chen, Ling AU - Chen L FAU - Cao, Ya-Ling AU - Cao YL FAU - Fang, Dian-Chun AU - Fang DC FAU - Yang, Shi-Ming AU - Yang SM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110419 PL - United States TA - Cancer Prev Res (Phila) JT - Cancer prevention research (Philadelphia, Pa.) JID - 101479409 RN - 0 (Antigens) RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes) RN - 0 (Peptides) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.2.1.- (heparanase) RN - EC 3.2.1.31 (Glucuronidase) SB - IM MH - Animals MH - Antigens/*chemistry MH - Antigens, Neoplasm/chemistry MH - Bone Marrow/metabolism MH - Cell Line, Tumor MH - Enzyme-Linked Immunosorbent Assay/methods MH - Epitopes/chemistry MH - Glucuronidase/*immunology MH - Hep G2 Cells MH - Humans MH - Immune System MH - Immunotherapy/methods MH - Interferon-gamma/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neoplasms/*immunology MH - Peptides/*chemistry MH - T-Lymphocytes, Cytotoxic/cytology EDAT- 2011/04/21 06:00 MHDA- 2012/01/06 06:00 CRDT- 2011/04/21 06:00 PHST- 2011/04/21 06:00 [entrez] PHST- 2011/04/21 06:00 [pubmed] PHST- 2012/01/06 06:00 [medline] AID - 1940-6207.CAPR-11-0083 [pii] AID - 10.1158/1940-6207.CAPR-11-0083 [doi] PST - ppublish SO - Cancer Prev Res (Phila). 2011 Aug;4(8):1285-95. doi: 10.1158/1940-6207.CAPR-11-0083. Epub 2011 Apr 19.