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Protein-Engineered Radiometal Chelates for Immunotherapy of Breast Cancer

机译：蛋白质工程Radiometal螯合物用于乳腺癌的免疫治疗

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The objective of this project has been to genetically engineer a radiometal binding site in a human antibody constant region, for eventual use in tumor radioimmunotherapy. Our molecular model system was a humanized anti-lysozyme antibody Fab fragment expressed in E. coil. The engineered binding site,consisting of 5 point mutations in the interior of the human Ck domain, destabilized the recombinant protein, leading to proteolysis. We attempted to address this problem by modifying the binding site design, expressing the protein within protease-negative host strains, and subcloning disulfide oxido- reductases into our expression vector, but none of these strategies resulted in a workable yield of recombinant protein. In collateral experiments, we characterized the three-dimensional structure of the anti-lysozyme.

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