title: Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II.
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.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA ; School of Medicine, Department of Medical Biology, Genome and Stem Cell Research Center, Erciyes University, 38039 Kayseri, Turkey.
authors.forename: Cagri
authors.initials: C
authors.lastname: Sakalar
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Suparna
authors.initials: S
authors.lastname: Mazumder
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA ; Department of Biology, Cleveland State University, Cleveland, OH, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Johnson
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA ; North American University, Texas Institute of Biotechnology, Education, and Research, 10555 Stella Link Road, No. 102, Houston, TX 77025, USA.
authors.forename: Cengiz Z
authors.initials: CZ
authors.lastname: Altuntas
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Ritika
authors.initials: R
authors.lastname: Jaini
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA ; Department of Biology, Cleveland State University, Cleveland, OH, USA ; Western Reserve Academy, Hudson, OH, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Aguilar
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Sathyamangla V
authors.initials: SV
authors.lastname: Naga Prasad
authors.affiliation: Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Connolly
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA ; Department of Biology, Cleveland State University, Cleveland, OH, USA ; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Vincent K
authors.initials: VK
authors.lastname: Tuohy
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009368:Neoplasm Transplantation; D009869:Oophoritis / Q000209:etiology / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D015202:Protein Engineering; D017434:Protein Structure, Tertiary / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage*
chemical_list: D019496:Cancer Vaccines; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C084621:anti-Mullerian hormone receptor