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

• Published in: Journal of Immunology Research Vol. 2015; no. 2015; pp. 1 - 13
• Main Authors: Tuohy, Vincent K., Connolly, Denise C., Aguilar, Robert, Jaini, Ritika, Altuntas, Cengiz Z., Johnson, Justin M., Mazumder, Suparna, Sakalar, Cagri, Prasad, Sathyamangla V. Naga
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2015; John Wiley & Sons, Inc; Hindawi Limited; Wiley
• Subjects: Adoptive Transfer; Animals; Antigens; Biotechnology; Cancer vaccines; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; Carcinoma - genetics; Carcinoma - immunology; Carcinoma - prevention & control; Cardiology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - transplantation; Cell Growth Processes; Cell Line, Tumor; Cells, Cultured; Epidermal growth factor; Epithelial Cells - physiology; Female; Gene expression; Genetic aspects; Humans; Immunology; Immunotherapy; Kinases; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Targeted Therapy; Neoplasm Transplantation; Oophoritis - etiology; Oophoritis - prevention & control; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - immunology; Ovarian Neoplasms - prevention & control; Physiological aspects; Prevention; Protein Engineering; Protein folding; Protein Structure, Tertiary - genetics; Receptors, Peptide - genetics; Receptors, Peptide - metabolism; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Recombinant Proteins - administration & dosage; T cell receptors; Transgenic animals; Tumors; Vaccination; United States; Cleveland Ohio; United States > US
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2015/630287

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.