The long-term objective of this project is to develop the means to utilize bi-specific immunoproteins for the selective concentration of boron-10 atoms in tumors for the boron neutron capture therapy (BNCT) of cancer. The bi-specific immunoproteins to be investigated in this project will have specificity for both a tumor-associated antigen (CEA) and a nido-carboranyl hapten. The project is focused on the development of methods for the expression of bi-specific immunoproteins using a genetic engineering approach. The genes encoding the anti-nido antibody and anti-CEA antibody are now available for manipulation. While performing research aimed at the development of optimal bi-specific immunoprotein delivery systems, the applicants intend to also conduct research aimed at developing optimal corresponding boron-rich hapten-containing macro molecules. The boron-rich macro molecules to be investigated will be based upon either a phosphate diester or polypeptide backbone. The applicants have developed flexible and efficient methods for the syntheses of both of these types of compounds, which can contain numerous hapten-like nido-carboranyl residues. The applicants will investigate whether these compounds can localize in tumor by pre-targeting bi-specific immunoprotein to tumor cells in vivo and then administering boron-rich macro molecules. This approach will be evaluated against one in which the macro molecules will be pre-bound to the bi-specific antibody and then subsequently administered in vivo. The anti-tumor efficacy of bi-specific antibodies in BNCT will be evaluated in mice bearing CEA+ and CEA- tumors.
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