A1 Refereed original research article in a scientific journal
A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3
Authors: Rahman NA, Bennink HJTC, Chrusciel M, Sharp V, Zimmerman Y, Dina R, Li XD, Ellonen A, Rivero-Muller A, Dilworth S, Ghaem-Maghami S, Vainio O, Huhtaniemi I
Publisher: FEDERATION AMER SOC EXP BIOL
Publication year: 2012
Journal: FASEB Journal
Journal name in source: FASEB JOURNAL
Journal acronym: FASEB J
Number in series: 1
Volume: 26
Issue: 1
First page : 324
Last page: 333
Number of pages: 10
ISSN: 0892-6638
DOI: https://doi.org/10.1096/fj.11-192468
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-alpha promoter (inh alpha/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/vehicletreated 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.-Rahman, N. A., Coelingh Bennink, H. J. T., Chrusciel, M., Sharp, V., Zimmerman, Y., Dina, R., Li, X., Ellonen, A., Rivero-Muller, A., Dilworth, S., Ghaem-Maghami, S., Vainio, O., Huhtaniemi, I. A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3. FASEB J. 26, 324-333 (2012). www.fasebj.org
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-alpha promoter (inh alpha/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/vehicletreated 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.-Rahman, N. A., Coelingh Bennink, H. J. T., Chrusciel, M., Sharp, V., Zimmerman, Y., Dina, R., Li, X., Ellonen, A., Rivero-Muller, A., Dilworth, S., Ghaem-Maghami, S., Vainio, O., Huhtaniemi, I. A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3. FASEB J. 26, 324-333 (2012). www.fasebj.org
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