Preparation and properties of nido-carborane-specific monoclonal antibodies for potential use in boron neutron capture therapy for cancer.
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.
Pak
R H
RH
Department of Chemistry and Biochemistry, University of California at Los Angeles 90024, USA.
Primus
F J
FJ
Rickard-Dickson
K J
KJ
Ng
L L
LL
Kane
R R
RR
Hawthorne
M F
MF
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
C094816:4-(7,8-dicarbadodecahydroundecaborat(-1)-7-yl)butanoic acid; D000911:Antibodies, Monoclonal; D001880:Boranes; D002087:Butyrates; D004337:Drug Carriers; D006241:Haptens