title: Heparanase DNA vaccine delivered by electroporation induces humoral immunity and cytoimmunity in animal models.
abstract: Electroporation (EP)-assisted DNA vaccination has been proven effective as an approach to the treatment of cancer. Although heparanase (HPA) is a potential target for patients with advanced tumor diseases, the efficacy of immunotherapeutic strategies targeting HPA has never been evaluated. In this study, humoral immunity was elicited using genetic vaccinations between C57BL/6J mice and Macaca fascicularis. The immunized serum neutralized HPA activity and attenuated the invasion of B16 cells in vitro. In addition, T lymphocytes from the splenic cells of the immunized mice induced HPA-specific cytotoxic lymphocytes (CTLs), which verified cytoimmunity. Prophylactic vaccination significantly suppressed tumor growth and metastasis in vivo and prolonged the survival rate in tumor-bearing murine models. In addition, RT-PCR and Western blot analyses of the primary tumors indicated less proliferation and angiogenesis and more apoptosis in the HPA-immunization immunotherapy groups. Simultaneously, the levels of IL-2, IL-4, and IFN-γ were not significantly greater in the HPA-immunized group than in PBS controls. Thus, we conclude that the combination of an anti-HPA antibody and a CTL response in HPA-immunization gene therapy is enough to attenuate tumor growth and metastasis. This is the first time that a DNA vaccine targeting HPA immunization assisted by EP has induced humoral immunity and cytoimmunity in vivo. This provides a basis for the continued development of DNA vaccines targeting HPA and the use of such vaccines in clinical settings.
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Bijun
authors.initials: B
authors.lastname: Zhao
authors.forename: Zhouhuan
authors.initials: Z
authors.lastname: Dong
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Haofei
authors.initials: H
authors.lastname: Luan
authors.forename: Xianfei
authors.initials: X
authors.lastname: Shen
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.forename: Feng
authors.initials: F
authors.lastname: Gong
authors.forename: Subo
authors.initials: S
authors.lastname: Li
authors.forename: Haifeng
authors.initials: H
authors.lastname: Song
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D018274:Electroporation / Q000379:methods*; D005260:Female; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D056724:Immunity, Humoral; D008252:Macaca fascicularis; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D009369:Neoplasms / Q000473:pathology / Q000517:prevention & control; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000099175:Heparanase
chemical_list: D057134:Antibodies, Neutralizing; D019496:Cancer Vaccines; D005966:Glucuronidase; D019444:Vaccines, DNA; D000099175:Heparanase