Our AEA™ Platform is a biologically engineered Chinese hamster ovary (“CHO”) cell line with the FUT8 knocked-out to generate antibodies with enhanced ADCC and improved antitumor activities. Through this bioengineering modification, the CHO cell line will not be able to catalyze the transfer of fucose residue from its donor to its target, and thus is not able to produce any antibody that carries fucose. Because absence of core fucose on the Fc region has been shown to increase the Fc region’s binding affinity to its receptor FcRIIIa present on immune effector cells, fucose-negative antibodies are expected to have enhanced ADCC activities through better activating immune effector cells. Accordingly, AEA™ Platform is expected to produce antibodies with 0% of fucose, which rapidly, stably, and thoroughly enhances the ADCC of antibodies and simplifies the quality control of the products. Therefore, AEA™ Platform can enable us to engineer any antibody or antibody portion (containing a Fc region) of biologics into ADCC enhanced products for enhanced immune effector cells activities.
SunHo ADCC Enhanced Antibody Platform, AEA™
Top left: Kubota et al, Cancer Sci (2009); top right: Yu et al, BioDrugs (2017)
The feasibility and advantages of AEA™ Platform have been demonstrated by IAH0968, the potential first complete fucose-removal anti-HER2-antibody in clinical stage developed through this platform. We have verified through glycoprotein detection and glycosylation quantification that IAH0968 does not contain any fucose. In addition, in vitro and in vivo tests showed that the affinity between IAH0968 and its Fc receptor was 10-20 times higher than unmodified or the other ADCC enhanced anti-HER2 antibodies, resulting in greater enhanced ADCC activity and antitumor efficacy.