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Sakalar C , Mazumder S , Johnson JM , Altuntas CZ , Jaini R , Aguilar R , Naga Prasad SV , Connolly DC , Tuohy VK
Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Mullerian Hormone Receptor II
J Immunol Res. 2015 ;2015 :630287
PMID: 26618181    PMCID: PMC4651663   
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Anti-Mullerian 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.
Sakalar, Cagri Mazumder, Suparna Johnson, Justin M Altuntas, Cengiz Z Jaini, Ritika Aguilar, Robert Naga Prasad, Sathyamangla V Connolly, Denise C Tuohy, Vincent K Egypt J Immunol Res. 2015;2015:630287. doi: 10.1155/2015/630287. Epub 2015 Nov 5.