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 bispecif ic monoclonal antibody system for the delivery of boron-rich molecules to tumor cells for boron neutron capture therapy, monoclonal antibodi es (mAbs) were produced against an anionic nido-carborane derivative, ,8-dicarbadodecahydroundecaborat(-1)-7-yl]butanoic acid. Two IgG subcl ass mAbs, designated HAW101 and HAW102, were identified that specifica lly bound the anionic nido-carborane hapten, as well as a variety of o ther anionic nido-carborane cage derivatives, By using surface plasmon resonance technology, the affinity constants of HAW101 and HAW102 wer e 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-carb orane derivatives reacted with the mAb HAW101 in competition ELISA, wh ereas anionic closo-polyhedral boranes showed negligible binding, sugg esting a role for the open nido-carborane cage structure. These result s suggest that mAbs such as HAW101, which bind anionic nido-carboranes , are useful in the development of bispecific mAbs for specific target ing and enhanced boron delivery to tumor sites.