Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II
Anti-Müllerian hormone receptor, type II (AMHR2), is a differentiation protein expressed in 90% of primary epithelial ovarian carcinomas (EOCs), the most deadly gynecologic malignancy. We propose that AMHR2 may serve as a useful target for vaccination against EOC. To this end, we generated the recom...
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/630287 |
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| author | Cagri Sakalar Suparna Mazumder Justin M. Johnson Cengiz Z. Altuntas Ritika Jaini Robert Aguilar Sathyamangla V. Naga Prasad Denise C. Connolly Vincent K. Tuohy |
| author_facet | Cagri Sakalar Suparna Mazumder Justin M. Johnson Cengiz Z. Altuntas Ritika Jaini Robert Aguilar Sathyamangla V. Naga Prasad Denise C. Connolly Vincent K. Tuohy |
| author_sort | Cagri Sakalar |
| collection | DOAJ |
| description | Anti-Müllerian hormone receptor, type II (AMHR2), is a differentiation protein expressed in 90% of primary epithelial ovarian carcinomas (EOCs), the most deadly gynecologic malignancy. We propose that AMHR2 may serve as a useful target for vaccination against EOC. To this end, we generated the recombinant 399-amino acid cytoplasmic domain of mouse AMHR2 (AMHR2-CD) and tested its efficacy as a vaccine target in inhibiting growth of the ID8 transplantable EOC cell line in C57BL/6 mice and in preventing growth of autochthonous EOCs that occur spontaneously in transgenic mice. We found that AMHR2-CD immunization of C57BL/6 females induced a prominent antigen-specific proinflammatory CD4+ T cell response that resulted in a mild transient autoimmune oophoritis that resolved rapidly with no detectable lingering adverse effects on ovarian function. AMHR2-CD vaccination significantly inhibited ID8 tumor growth when administered either prophylactically or therapeutically, and protection against EOC growth was passively transferred into naive recipients with AMHR2-CD-primed CD4+ T cells but not with primed B cells. In addition, prophylactic AMHR2-CD vaccination of TgMISIIR-TAg transgenic mice significantly inhibited growth of autochthonous EOCs and provided a 41.7% increase in mean overall survival. We conclude that AMHR2-CD vaccination provides effective immunotherapy of EOC with relatively benign autoimmune complications. |
| format | Article |
| id | doaj-art-84bb0ef9ac804454a7ac3b4d21dfd3fa |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-84bb0ef9ac804454a7ac3b4d21dfd3fa2025-02-03T01:32:18ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/630287630287Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor IICagri Sakalar0Suparna Mazumder1Justin M. Johnson2Cengiz Z. Altuntas3Ritika Jaini4Robert Aguilar5Sathyamangla V. Naga Prasad6Denise C. Connolly7Vincent K. Tuohy8Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADevelopmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USADepartment of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USAAnti-Müllerian hormone receptor, type II (AMHR2), is a differentiation protein expressed in 90% of primary epithelial ovarian carcinomas (EOCs), the most deadly gynecologic malignancy. We propose that AMHR2 may serve as a useful target for vaccination against EOC. To this end, we generated the recombinant 399-amino acid cytoplasmic domain of mouse AMHR2 (AMHR2-CD) and tested its efficacy as a vaccine target in inhibiting growth of the ID8 transplantable EOC cell line in C57BL/6 mice and in preventing growth of autochthonous EOCs that occur spontaneously in transgenic mice. We found that AMHR2-CD immunization of C57BL/6 females induced a prominent antigen-specific proinflammatory CD4+ T cell response that resulted in a mild transient autoimmune oophoritis that resolved rapidly with no detectable lingering adverse effects on ovarian function. AMHR2-CD vaccination significantly inhibited ID8 tumor growth when administered either prophylactically or therapeutically, and protection against EOC growth was passively transferred into naive recipients with AMHR2-CD-primed CD4+ T cells but not with primed B cells. In addition, prophylactic AMHR2-CD vaccination of TgMISIIR-TAg transgenic mice significantly inhibited growth of autochthonous EOCs and provided a 41.7% increase in mean overall survival. We conclude that AMHR2-CD vaccination provides effective immunotherapy of EOC with relatively benign autoimmune complications.http://dx.doi.org/10.1155/2015/630287 |
| spellingShingle | Cagri Sakalar Suparna Mazumder Justin M. Johnson Cengiz Z. Altuntas Ritika Jaini Robert Aguilar Sathyamangla V. Naga Prasad Denise C. Connolly Vincent K. Tuohy Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II Journal of Immunology Research |
| title | Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II |
| title_full | Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II |
| title_fullStr | Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II |
| title_full_unstemmed | Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II |
| title_short | Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II |
| title_sort | regulation of murine ovarian epithelial carcinoma by vaccination against the cytoplasmic domain of anti mullerian hormone receptor ii |
| url | http://dx.doi.org/10.1155/2015/630287 |
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