title: The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity.
abstract: Because of its high mortality rate, ovarian cancer is a leading cause of death among women and a highly unmet medical need. New therapeutic agents that are effective and well tolerated are needed and cancer antigen-specific monoclonal antibodies that have direct pharmacologic effects or can stimulate immunological responses represent a promising class of agents for the treatment of this disease. The human folate receptor α (FOLR1), which is overexpressed in ovarian cancer but largely absent in normal tissues, appears to play a role in the transformed phenotype in ovarian cancer, cisplatin sensitivity, and growth in depleted folate conditions and therefore has potential as a target for passive immunotherapy. The anti-FOLR1 monoclonal antibody MORAb-003 (farletuzumab) was previously shown to elicit antibody dependent cellular cytotoxicity (ADCC) and inhibit tumor growth of human tumor xenografts in nude mice. Because of its promising preclinical profile, farletuzumab has been evaluated in clinical trials as a potential therapeutic agent for ovarian cancer. In this report, we demonstrated that farletuzumab's antitumor effect against an experimental model of ovarian cancer is mediated by its ADCC activity.
authors.affiliation: Morphotek Inc.; Exton, PA USA.
authors.forename: JianMin
authors.initials: J
authors.lastname: Lin
authors.forename: Jared L
authors.initials: JL
authors.lastname: Spidel
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Maddage
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Rybinski
authors.forename: Rina P
authors.initials: RP
authors.lastname: Kennedy
authors.forename: Candice L M
authors.initials: CL
authors.lastname: Krauthauser
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Park
authors.forename: Earl F
authors.initials: EF
authors.lastname: Albone
authors.forename: Sara
authors.initials: S
authors.lastname: Jacob
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Goserud
authors.forename: Bryon P
authors.initials: BP
authors.lastname: Martinez
authors.forename: Qimin
authors.initials: Q
authors.lastname: Chao
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Nicolaides
authors.forename: J Bradford
authors.initials: JB
authors.lastname: Kline
authors.forename: Luigi
authors.initials: L
authors.lastname: Grasso
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D058975:Folate Receptor 1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C496124:FCGR3A protein, human; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D017452:Receptors, IgG; C527484:farletuzumab
keywords: CD16a; FOLR1; antibody-dependent cellular cytotoxicity; farletuzumab; ovarian cancer
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