Pretargeting approaches have been considered to overcome problems associated with conventional radioimmunotherapy (RAIT) where the radionuclide is attached to the antibody. Most pretargeting studies employ an avidin/biotin recognition system. Even though clinical trials are providing encouraging results, (strept) avidin has been found to be highly immunogenic and endogenous biotin has been shown to interfere with targeting. The use of oligomers in place of biotin and (strept) avidin for pretargeting localization has the potential to eliminate these problems. Oligomers bind with high affinity and specificity to their complement and there is no endogenous oligomer problem. Oligomeric phophodiester and phosphorothioate DNAs have been considered for pretargeting, and found to be unsuitable due to rapid in vivo degradation of the former and the great tendency of the latter to bind to normal tissues. Peptide nucleic acids (PNAs) are proposed here as the novel recognition system for a pretargeting approach where PNA will be conjugated to an antibody. After clearing unbound circulating antibody with an anti-idiotypic antibody, radionuclide will be delivered via the complimentary strand of PNA. Ultimately, a pretargeting system comprising solely cdr-grated targeting and clearance antibodies is envisaged.
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