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 language | English |
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Article number | 630287 |
Pages (from-to) | 630287 |
Journal | Journal of Immunology Research |
Volume | 2015 |
DOIs | |
State | Published - 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