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Anti-Müllerian hormone receptor type 2 (AMHR2) is a transmembrane serine/threonine kinase receptor belonging to the transforming growth factor-beta (TGF-beta) receptor family [1]. It serves as the primary receptor for Anti-Müllerian hormone (AMH), a signaling protein essential for the regression of Müllerian ducts in male embryos [1, 4]. In adult females, AMHR2 is expressed in granulosa cells where it regulates the recruitment and maturation of ovarian follicles [4]. The receptor is notably overexpressed in approximately 70-90% of epithelial ovarian cancers and other gynecological malignancies, such as endometrial and cervical cancers [2, 4]. Because its expression in healthy adult tissues is highly restricted to the gonads, AMHR2 is considered a promising target for tumor-specific immunotherapy [2, 3]. The 4D12G1 epitope is a specific region on the extracellular domain (ED) of AMHR2 recognized by the monoclonal antibody clone 4D12G1 (also known as 12G1) [2]. Therapeutic agents targeting this epitope, such as the humanized antibody 3C23K and the glyco-engineered version GM102, primarily act through antibody-dependent cellular cytotoxicity (ADCC) to eliminate malignant cells [2, 3]. These drugs are designed to provide a targeted treatment option for patients with AMHR2-positive tumors, potentially minimizing the systemic toxicity associated with conventional chemotherapy [3]. Sources: [1] UniProt Consortium. "AMHR2 - Anti-Müllerian hormone type II receptor." UniProtKB - Q16671. [2] Kersual, N., et al. "The Anti-Müllerian Hormone Type II Receptor as a New Target for Ovarian Cancer Immunotherapy." Frontiers in Oncology, 2014. (PMID: 24714539). [3] GamaMabs Pharma. "Pipeline: AMHR2-targeting antibodies." Corporate Website. [4] Bakkum-Gamez, J. N., et al. "Müllerian inhibiting substance type II receptor (MISIIR): a novel target for therapy in gynecologic cancers." Gynecologic Oncology, 2008. (PMID: 18348157).
Antibody-dependent cellular cytotoxicity (ADCC) and inhibition of AMH-mediated signaling
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