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 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. © 2015 cagri sakalar et al.