A mAb against surface-expressed FSHR engineered to engage adaptive immunity for ovarian cancer immunotherapy

• DOI: 10.1172/jci.insight.162553
• Publication Date: 2022-11-21T19:01:06Z
• Authors: Devivasha Bordoloi; Pratik S. Bhojnag...; Alfredo Perales-P...; Abhijeet J. Kulkarni; Xizhou Zhu; Kevin Liaw; Ryan P. O’Connell; Daniel H. Park; Daniel W. Kulp; Rugang Zhang; David B. Weiner
• Keywords: Follicle-stimulating hormone receptor

Despite advances in ovarian cancer (OC) therapy, recurrent OC remains a poor-prognosis disease. Because of the close interaction between cells and tumor microenvironment (TME), it is important to develop strategies that target engage components TME. A major obstacle development therapies identification targets with expression limited surface avoid off-target interactions. The follicle-stimulating hormone receptor (FSHR) has selective on granulosa expressed 50%-70% serous OCs. We generated mAbs targeting external domain FSHR using vivo-expressed vector. By high-throughput flow analysis, we identified multiple clones downselected D2AP11, potent surface-targeted mAb. D2AP11 identifies cell lines derived from tumors different mutations, including BRCA1/2, resistant wide range therapies. used bispecific T engager. In vitro addition PBMCs D2AP11-TCE induced specific killing genetic immune escape lines, EC50s ng/ml range, attenuated burden OC-challenged mouse models. These studies demonstrate potential utility biologics for perhaps other FSHR-positive cancers.