title: A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3.
abstract: We tested the principle of treating malignant ovarian tumors by vaccination against their ectopically expressed protein, zona pellucida glycoprotein (ZP) 3, using as the experimental model the granulosa cell tumors that develop in transgenic mice expressing the simian virus 40 T-antigen under the inhibin-α promoter (inhα/Tag). We found high ZP3 expression in granulosa cell tumors of the transgenic mice, in human surface ovarian cancer and granulosa cell lines, and in human granulosa cell tumors and their metastases. Early preventive immunization (between 2 and 5.5 mo of age) of transgenic mice with recombinant human (rh) ZP3 prevented ovarian tumorigenesis, and delayed therapeutic immunization (between 4.5 and 7 mo) reduced weights of existing tumors by 86 and 75%, respectively (P<0.001), compared to vehicle-treated control mice. No objective side effects of the immunizations were observed. Liver metastases were found in nontreated/vehicle-treated controls (n=7/39), but none following active rhZP3 immunizations (n=0/36; P<0.05). Immunization with rhZP3 was highly effective, as demonstrated by the induction of anti-ZP3 antibodies, as well as proliferative responses to the ZP3 antigen. These results signal rhZP3 immunization as a novel strategy to be developed for the immunotherapy of ovarian granulosa cell tumors, as well as for that of other malignancies that may express ZP3.
authors.affiliation: Department of Physiology, University of Turku, Turku, Finland. nafis.rahman@utu.fi
authors.forename: Nafis A
authors.initials: NA
authors.lastname: Rahman
authors.forename: Herjan J T Coelingh
authors.initials: HJ
authors.lastname: Bennink
authors.forename: Marcin
authors.initials: M
authors.lastname: Chrusciel
authors.forename: Victoria
authors.initials: V
authors.lastname: Sharp
authors.forename: Yvette
authors.initials: Y
authors.lastname: Zimmerman
authors.forename: Roberto
authors.initials: R
authors.lastname: Dina
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
authors.forename: Antti
authors.initials: A
authors.lastname: Ellonen
authors.forename: Adolfo
authors.initials: A
authors.lastname: Rivero-Müller
authors.forename: Stephen
authors.initials: S
authors.lastname: Dilworth
authors.forename: Sadaf
authors.initials: S
authors.lastname: Ghaem-Maghami
authors.forename: Olli
authors.initials: O
authors.lastname: Vainio
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004527:Egg Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006106:Granulosa Cell Tumor / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D006801:Humans; D007114:Immunization / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010051:Ovarian Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D015044:Zona Pellucida / Q000276:immunology* / Q000378:metabolism; D000072216:Zona Pellucida Glycoproteins
chemical_list: D000951:Antigens, Neoplasm; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse