A methodology has been developed for the preparation of well-defined antibody-drug conjugates (ADC) by glycan remodeling using CMP-Neu5Ac modified by a clickable group such as azide.  The latter moiety makes it possible to attach various cytotoxic drugs in a site-specific manner. The methodology was employed to develop ADCs that selectively can kill lymphoma cells that overexpress CD22. It has been shown that the conjugation methodology does not interfere with antibody effector functions. The new method for homogenous ADC production is attractive because it does not require genetic engineering, and therefore is applicable to any type of therapeutic antibody. The new site-specific coupling methodologies make it possible to improve properties of protein conjugates by structure-function relationships in a medical chemistry like fashion.

Preparation of well-defined antibody-drug conjugates through glycan remodeling and strain promoted azide-alkyne cycloadditions

251st National Meeting (2016)

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