Engineered Cysteine Drug Conjugates Show Potency And Improved Safety

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Antibody-drug conjugates (ADCs) are emerging as an important therapeutic option for new oncology drugs. In this abstract we present data on engineered cysteine antibodies (EC-mAbs) with an additional unpaired cysteine residue introduced at position 239 on each heavy chain to facilitate more uniform drug loading while interfering with Fc gamma receptor function. With the EC-mAb, we have identified a site that blocks Fc gamma receptor III (CD16) binding and has a number of additional desirable biochemical and biophysical properties. We demonstrate that EC-mAb-drug conjugates, with two drugs per antibody, retain antitumor activity in mouse xenograft experiments and are well tolerated in non-human primates. These data suggest that engineered cysteine antibodies are a potential alternative to conjugation of native cysteines for future ADCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4634. doi:1538-7445.AM2012-4634