title: Preclinical evaluation of MORAb-003, a humanized monoclonal antibody antagonizing folate receptor-alpha.
abstract: The highly restricted distribution of human folate receptor-alpha (FRalpha) in normal tissues and its high expression in some tumors, along with its putative role in tumor cell transformation, make this antigen a suitable target for antigen-specific, monoclonal antibody-based immunotherapy for oncology indications. We have developed a therapeutic humanized monoclonal antibody with high affinity for FRalpha, named MORAb-003, which was derived from the optimization of the LK26 antibody using a whole cell genetic evolution platform. Here we show that MORAb-003 possesses novel, growth-inhibitory functions on cells overexpressing FRalpha. In addition, MORAb-003 elicited robust antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in vitro, and inhibited growth of human ovarian tumor xenografts in nude mice. Because of its multimodal activity in vitro and its safe toxicology profile in non-human primates, MORAb-003 development has recently been advanced to clinical trials involving ovarian cancer patients.
authors.affiliation: Morphotek Inc., 210 Welsh Pool Road, Exton, PA, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ebel
authors.forename: Eric L
authors.initials: EL
authors.lastname: Routhier
authors.forename: Brian
authors.initials: B
authors.lastname: Foley
authors.forename: Sara
authors.initials: S
authors.lastname: Jacob
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: McDonough
authors.forename: Rina K
authors.initials: RK
authors.lastname: Patel
authors.forename: Howard A
authors.initials: HA
authors.lastname: Turchin
authors.forename: Qimin
authors.initials: Q
authors.lastname: Chao
authors.forename: J Bradford
authors.initials: JB
authors.lastname: Kline
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Martin D
authors.initials: MD
authors.lastname: Phillips
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Nicolaides
authors.forename: Philip M
authors.initials: PM
authors.lastname: Sass
authors.forename: Luigi
authors.initials: L
authors.lastname: Grasso
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D016466:CHO Cells; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000276:immunology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011323:Primates / Q000276:immunology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; C079669:LK26 antigen; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface