2020 Volume 30 Issue 3 Pages 137-144
Antibody-drug conjugates (ADCs) have become a major class of cancer biopharmaceuticals and traditional ADCs have a stochastic distribution of cytotoxic drugs linked across several different sites of the antibody. The heterogeneous nature of resulting stochastic ADCs can cause diminished efficacy and increased toxicity, thus limiting the corresponding therapeutic index. To improve on traditional ADC technology, we developed and report here a novel chemical conjugation platform termed “AJICAP™” for the site-specific modification of native antibodies through the use of a class of IgG Fc-affinity reagents. Site-specific installation of thiol functional groups to well-defined lysine residues in IgGs followed by conjugation to these newly installed thiols with cytotoxic payloads was efficiently conducted to generate AJICAP™-ADCs. Several results described that AJICAP™-ADCs expand the therapeutic window compare to random conjugated ADCs. AJICAP™ technology is a powerful platform to enable next-generation ADCs through the reduction of heterogeneity and enhanced of therapeutic index.
