Abstract B204: Engineered cysteine antibodies: Improved antibody-drug conjugate vehicles.

The use of monoclonal antibodies for the delivery of anticancer drugs to tumor cells is an emerging therapeutic modality and has been the subject of a great deal of investigation. In this study we have engineered antibody variants with an additional cysteine residue in the each heavy chain to provide a route towards homogenous two drugs per antibody loading while interfering with Fc gamma receptor binding. We have characterized the relationship between the site of drug conjugation and a number of key parameters including relative protein expression, conjugatability, drug-linker stability, effects on biophysical properties of the resulting antibody-drug conjugate (ADC), and in vitro cytotoxicity. We demonstrate that the site of conjugation affects many of these parameters and that Engineered Cysteine (EC) antibodies can be considered a viable next generation ADC approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B204.