PROJECT TITLE: FURTHER EVALUATION OF AMHR2-ED ANTIGENS FOR EPITHELIAL OVARIAN CARCINOMA
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Principal Investigator: CHINTHALAPALLY RAO Organization: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR Fiscal Year: 2021 Award: $845,841 Funding agency: National Cancer Institute It has been shown that the extracellular domain of human anti-Müllerian hormone receptor type II (AMHR2-ED) is a prototypic ‘retired’ tissue-specific protein that may serve as a vaccine target for primary immunoprevention of epithelial ovarian cancer. AMHR2 is a serine/threonine kinase receptor homologous to type II receptors of the transforming growth factor-beta (TGFβ) superfamily. Anti-Müllerian hormone (AMH) is the cognate ligand of AMHR2-ED, and binding of AMH to AMHR2-ED signals cell cycle arrest and programmed cell death resulting in regression of the Müllerian ducts during male development and regulation of oocyte development, and control of ovarian reserve and fertility in adult females. In adult women, the longest AMHR2 transcript codes for a 573 amino acid protein expressed exclusively in the ovary and contains a 127 amino acid AMHR2-ED ligand-binding domain expressed exclusively in the human ovary along with a 26 amino acid transmembrane domain and a 403 amino acid cytoplasmic kinase domain (AMHR2-CD) both of which show extra-ovarian expression. The PREVENT program has chosen to support the development of protein and mRNA AMHR2-E2 vaccines to assess their efficacy in preclinical mouse models. In support of this project, PREVENT has initiated contract work with two specific aims. Terms: <21+ years old><AMH Type II Receptor><AMHR><AMHR2><AMHR2 gene><Adult><Adult Human><Amino Acids><Anti-Mullerian Hormone Receptor Type II><Antigens><Apoptosis><Apoptosis Pathway><Binding><Binding Site Domain><Body Tissues><Cell Communication and Signaling><Cell Cycle Arrest><Cell Signaling><Code><Coding System><Contracting Opportunities><Contracts><Development><Epithelial><Epithelial ovarian cancer><Evaluation><External Domain><Extracellular Domain><Fecundability><Fecundity><Female><Fertility><Human><Immunoprevention><Intracellular Communication and Signaling><Kinases><Ligand Binding Domain><Ligands><MIS Type II Receptor><MISRII><MRII><Malignant Ovarian Neoplasm><Malignant Ovarian Tumor><Malignant Tumor of the Ovary><Malignant neoplasm of ovary><Messenger RNA><Modern Man><Molecular Interaction><Muellerian inhibiting hormone><Mullerian Ducts><Mullerian-inhibiting factor><Mullerian-inhibiting substance type II receptor><Oocytes><Ovarian><Ovarian Carcinoma><Ovary><Ovary Cancer><Ovary Carcinoma><Ovocytes><Paramesonephric Duct><Phosphotransferase Gene><Phosphotransferases><Programmed Cell Death><Proteins><RNA vaccine><RNA-based vaccine><Receptor Serine/Threonine Kinase><Regulation><STKRP><Signal Transduction><Signal Transduction Systems><Signaling><Structure of paramesonephric duct><TGF-Beta Type II Receptor><TGFBR2><TGFBR2 gene><TM Domain><Tissues><Transcript><Transgenic Organisms><Transmembrane Domain><Transmembrane Region><Transphosphorylases><Type II Gene Anti-Mullerian Hormone Receptor><Vaccines><Woman><Work><adulthood><aminoacid><anti-mullerian factor><anti-mullerian hormone><antimullerian hormone><biological signal transduction><developmental><immunogen><immunogenicity><in vivo><mRNA><mRNA vaccine><mRNA-based vaccine><male><mouse model><mullerian inhibiting substance><mullerian regression factor><mullerian-inhibiting hormone><mullerian-inhibitory substance><murine model><ovarian cancer><ovarian reserve><pre-clinical><preclinical><programs><transforming growth factor-beta type II receptor><transforming growth factor-β type II receptor><transgenic>