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Journal of Immunology Research
Volume 2015 (2015), Article ID 630287, 13 pages
Research Article

Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II

1Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
2School of Medicine, Department of Medical Biology, Genome and Stem Cell Research Center, Erciyes University, 38039 Kayseri, Turkey
3Department of Biology, Cleveland State University, Cleveland, OH, USA
4North American University, Texas Institute of Biotechnology, Education, and Research, 10555 Stella Link Road, No. 102, Houston, TX 77025, USA
5Western Reserve Academy, Hudson, OH, USA
6Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
7Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA
8Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA

Received 16 July 2015; Accepted 12 October 2015

Academic Editor: Fabio Pastorino

Copyright © 2015 Cagri Sakalar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.