HOMOGENEOUS IMMUNOCONJUGATES FOR BORON NEUTRON-CAPTURE THERAPY - DESIGN, SYNTHESIS, AND PRELIMINARY CHARACTERIZATION

The application of immunoprotein-based targeting strategies to the bor on neutron-capture therapy of cancer poses an exceptional challenge, b ecause viable boron neutron-capture therapy by this method will requir e the efficient delivery of 10(3) boron-10 atoms by each antigen-bindi ng protein. Our recent investigations in this area have been focused o n the development of efficient methods for the assembly of homogeneous immunoprotein conjugates containing the requisite boron load. In this regard, engineered immunoproteins fitted with unique, exposed cystein e residues provide attractive vehicles for site-specific modification, Additionally, homogeneous oligomeric boron-rich phosphodiesters (olig ophosphates) have been identified as promising conjugation reagents, T he coupling of two such boron-rich oligophosphates to sulfhydryls intr oduced to the C(H)2 domain of a chimeric IgG3 has been demonstrated. T he resulting boron-rich immunoconjugates are formed efficiently, are r eadily purified, and have promising in vitro and in vivo characteristi cs. Encouragingly, these studies showed subtle differences in the prop erties of the conjugates derived from the two oligophosphate molecules studied, providing a basis for the application of rational design to future work Such subtle details would not have been as readily discern ible in heterogeneous conjugates, thus validating the rigorous experim ental design employed here.