Anti-M�¨ullerian hormone receptor, type II (AMHR2), is a differentiation protein expressed in 90% of primary epithelial ovarian\ncarcinomas (EOCs), the most deadly gynecologic malignancy.We propose that AMHR2 may serve as a useful target for vaccination\nagainst EOC. To this end, we generated the recombinant 399-amino acid cytoplasmic domain of mouse AMHR2 (AMHR2-\nCD) and tested its efficacy as a vaccine target in inhibiting growth of the ID8 transplantable EOC cell line in C57BL/6 mice\nand in preventing growth of autochthonous EOCs that occur spontaneously in transgenic mice. We found that AMHR2-CD\nimmunization of C57BL/6 females induced a prominent antigen-specific proinflammatory CD4+ T cell response that resulted\nin a mild transient autoimmune oophoritis that resolved rapidly with no detectable lingering adverse effects on ovarian function.\nAMHR2-CD vaccination significantly inhibited ID8 tumor growth when administered either prophylactically or therapeutically,\nand protection against EOC growth was passively transferred into naive recipients with AMHR2-CD-primed CD4+ T cells but not\nwith primed B cells. In addition, prophylactic AMHR2-CD vaccination of Tg MISIIR-TAg transgenic mice significantly inhibited\ngrowth of autochthonous EOCs and provided a 41.7% increase in mean overall survival.We conclude that AMHR2-CD vaccination\nprovides effective immunotherapy of EOC with relatively benign autoimmune complications
Loading....