Autoimmune mediated regulation of ovarian tumor growth.

ABSTRACT

OBJECTIVES: An immune response sufficient to induce organ failure may provide protection and therapy against tumors derived from the targeted organ particularly when removal or ablation of the organ is part of the standard therapy and does not threaten survival. We have previously shown that a targeted immune response directed against the ovarian-specific protein, inhibin-α, causes ovarian failure. Here we determined whether inhibin-α autoimmunity is effective in both prevention and treatment of ovarian tumors. METHODS: A transgene consisting of the SV40 large tumor transformation antigen under the regulation of an anti-Mullerian hormone promoter (AMH-SV40Tag) was transferred by backcrossing for 12 generations to SJL/J mice producing SJL.AMH-SV40Tag (H-2(s)) females that develop a high incidence of autochthonous granulosa cell tumors. We determined whether immunization of SJL.AMH-SV40Tag female mice with the IA(s)-restricted p215-234 peptide of mouse inhibin-α was capable of preventing and treating these ovarian tumors. RESULTS: The growth of autochthonous ovarian granulosa cell tumors in SJL.AMH-SV40Tag transgenic mice was significantly inhibited in mice immunized with Inα 215-234. In addition, significant inhibition of tumor growth occurred when mice with established ovarian granulosa cell tumors were therapeutically vaccinated with Inα 215-234. CONCLUSIONS: Our results indicate that induction of ovarian-specific autoimmunity may serve as an effective way to prevent the emergence of autochthonous ovarian tumors and control the growth of established ovarian malignancies.