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

Cagri Sakalar, Suparna Mazumder, Justin M. Johnson, Cengiz Z. Altuntas, Ritika Jaini, Robert Aguilar, Sathyamangla V.Naga Prasad, Denise C. Connolly, Vincent K. Tuohy

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Article number630287
Pages (from-to)630287
JournalJournal of Immunology Research
Volume2015
DOIs
StatePublished - 2015

Keywords

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes/immunology
  • Cancer Vaccines/administration & dosage
  • Carcinoma/genetics
  • Cell Growth Processes
  • Cell Line, Tumor
  • Cells, Cultured
  • Epithelial Cells/physiology
  • Female
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Targeted Therapy
  • Neoplasm Transplantation
  • Oophoritis/etiology
  • Ovarian Neoplasms/genetics
  • Protein Engineering
  • Protein Structure, Tertiary/genetics
  • Receptors, Peptide/genetics
  • Receptors, Transforming Growth Factor beta/genetics
  • Recombinant Proteins/administration & dosage

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