Antibody drug conjugates (ADCs) are a new therapeutic class offering a great promise for cancer therapy. The attachment of cytotoxic drugs to antibodies can result in a more effective therapy with better safety potential than non-targeted cytotoxics. To understand the role of the conjugation site, we developed an enzymatic method for site-specific antibody-drug conjugation using microbial transglutaminase. This approach enabled us to attach diverse compounds at multiple positions and investigate how the site of attachment influences stability, toxicity, and efficacy.  We show that the conjugation site has significant impact on ADC stability and pharmacokinetics in a species dependent manner. With this method, it is possible to produce homogeneous ADCs and tune their properties to maximize the therapeutic window.

Modulating properties of antibody drug conjugates with site specific conjugation

248th National Meeting (2014)

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