Methods for site-specific drug conjugation to antibodies |
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Authors: | Christopher R Behrens Bin Liu |
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Affiliation: | Department of Anesthesia; UCSF Helen Diller Family Comprehensive Cancer Center; University of California at San Francisco; San Francisco, CA USA |
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Abstract: | Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over traditional chemotherapy. Drugs and linkers have been the current focus of ADC development, in addition to antibody and target selection. Recently, however, the importance of conjugate homogeneity has been realized. The current methods for drug attachment lead to a heterogeneous mixture, and some populations of that mixture have poor in vivo performance. New methods for site-specific drug attachment lead to more homogeneous conjugates and allow control of the site of drug attachment. These subtle improvements can have profound effects on in vivo efficacy and therapeutic index. This review examines current methods for site-specific drug conjugation to antibodies, and compares in vivo results with their non-specifically conjugated counterparts. The apparent improvement in pharmacokinetics and the reduced off target toxicity warrant further development of this site-specific modification approach for future ADC development. |
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Keywords: | site-specific antibody drug conjugate ADC targeted cancer therapy therapeutic index THIOMAB transglutaminase unnatural amino acids |
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