Antibodies are being extensively investigated as in vivo diagnostic and therapeutic tools the for specific delivery of drugs, radionuclides or toxins to target tissue. This antibody mediated delivery is however inefficient resulting in only a fraction of the administered dose reaching the tissue. In addition antibody dependent delivery systems suffer from the inability to precisely control circulating half life of the complex, the inability to regulate the biodistribution of modified antibodies an the limited amounts of therapeutic or diagnostic agent which can be coupled to each antibody. Furthermore, the induction of an immune response to a foreign antibody has been reported to decrease or inactivate previously effective antibody reagents. Recent reports from this laboratory have demonstrated that it is possible to attain high degrees of modification of antibody molecules with water soluble polymers without loss of antigen binding activity. Thereby opening the possibility of using a polymer modification approach as a method to engineer specific properties into antibody molecules. The objective of the modifications being the design of therapeutic and diagnostic agents that 1) can be rapidly prepared, 2) have low or controllable immunogenicity, 3) can have well established biological properties with known biodistributions and circulating half life and 4) can be modified to carry a significant amount of the toxic agent. Students involved in this project will have their research focused in the areas of investigating the effects of covalent modification with polymers other than PEG and polymers of different sizes on the antigen binding activity, biodistribution and storage stability.
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