Sortase-mediated Antibody Conjugation (SMAC™): Generation of Homogeneous, Site-specifically Conjugated Antibody Drug Conjugates
Roger Beerli,
Chief Scientific Officer,
NBE Therapeutics
Antibody drug conjugates (ADCs) have recently been proven to be highly potent anti-tumor drugs, typically exceeding the efficacy of conventional monoclonal antibodies (mAbs). ADCs are currently produced by chemical conjugation of the small-molecule toxin to the mAb through lysine or cysteine side chains, leading to heterogeneous mixtures that present challenges with respect to analytical characterization and manufacturing. Furthermore, the individual components of these mixtures behave differently with respect to their pharmacokinetic, efficacy, and safety profiles. As a consequence, there is great interest in the further development of drug conjugation technologies, with a particular focus on site-specific payload conjugation. Here, we present an enzymatic conjugation platform called SMACTM (sortase-mediated antibody conjugation) technology that allows for efficient generation of homogeneous ADCs with pre-defined drug-to-antibody ratios. Data will be presented demonstrating that SMACTM technology is capable of producing homogeneous ADCs based on numerous toxic payloads, with high potencies for tumor cell killing in vitro and in vivo.
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