title: Preparation and properties of nido-carborane-specific monoclonal antibodies for potential use in boron neutron capture therapy for cancer.
abstract: As the first step of a research program aimed at developing a bispecific monoclonal antibody system for the delivery of boron-rich molecules to tumor cells for boron neutron capture therapy, monoclonal antibodies (mAbs) were produced against an anionic nido-carborane derivative, 4-[7,8-dicarbadodecahydroundecaborat(-1)-7-yl]butanoic acid. Two IgG subclass mAbs, designated HAW101 and HAW102, were identified that specifically bound the anionic nido-carborane hapten, as well as a variety of other anionic nido-carborane cage derivatives. By using surface plasmon resonance technology, the affinity constants of HAW101 and HAW102 were determined to be 1.9 x 10(9) and 6.8 x 10(8) M-1, respectively. A diverse array of 7-substituted and 7,8-disubstituted anionic nido-carborane derivatives reacted with the mAb HAW101 in competition ELISA, whereas anionic closo-polyhedral boranes showed negligible binding, suggesting a role for the open nido-carborane cage structure. These results suggest that mAbs such as HAW101, which bind anionic nido-carboranes, are useful in the development of bispecific mAbs for specific targeting and enhanced boron delivery to tumor sites.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at Los Angeles 90024, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Pak
authors.forename: F J
authors.initials: FJ
authors.lastname: Primus
authors.forename: K J
authors.initials: KJ
authors.lastname: Rickard-Dickson
authors.forename: L L
authors.initials: LL
authors.lastname: Ng
authors.forename: R R
authors.initials: RR
authors.lastname: Kane
authors.forename: M F
authors.initials: MF
authors.lastname: Hawthorne
mesh_terms: D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001667:Binding, Competitive; D001880:Boranes / Q000276:immunology*; D016754:Boron Neutron Capture Therapy; D002087:Butyrates / Q000276:immunology*; D004337:Drug Carriers; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens / Q000276:immunology; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D013329:Structure-Activity Relationship
chemical_list: C094816:4-(7,8-dicarbadodecahydroundecaborat(-1)-7-yl)butanoic acid; D000911:Antibodies, Monoclonal; D001880:Boranes; D002087:Butyrates; D004337:Drug Carriers; D006241:Haptens