Antibody-drug conjugates (ADCs) hold great promise to specifically deliver cytotoxic drugs to targets such as tumor cells, and as such, have become one of the fastest growing class of therapeutic agents. Covalent attachment of an organic cytotoxin to a monoclonal antibody, however, alters the stability of the protein conjugate. Despite the importance of this for manufacturing, processing, and storage of ADCs, the influences of conjugation on the physical stability of the protein have not been widely or systematically studied. Here, we present our investigation of a systematically modified Fc region of IgG1 using a set of fluorophores and characterize the relationship between the protein's physical stability and hydrophobicity and/or surface charge. The fluorophores were conjugated to Fc at Lys residues and the conjugates were characterized using chromatographic methods, including size-exclusion chromatography, ion exchange chromatography, and hydrophobic interaction chromatography, as well as differential scanning calorimetry, light scattering, and circular dichroism.

Investigation of the relationship between stability and chemical modification in Fc-conjugates

243rd National Meeting (2012)

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