Selective FcγR engagement by human agonistic anti-CD40 antibodies

Dahan et al. recently published a study where they investigated the influence of FcγRs on the activity of human monoclonal anti-CD40 antibodies using a mouse model with humanized FcγRs and CD40 (1). Using a humanized model system they elegantly demonstrate the importance of FcɣRIIB for optimal efficacy of human anti-CD40 antibodies. The results partly contrast previously published material (2-4) where the importance of FcɣRIIB is not unambiguous and is suggested to depend also on the antibody itself as well as the overall tissue expression load of the FcɣR family. If the data presented by Dahan et al. can be transferred and confirmed in un-modified in vitro human assays it could impact the design of TNFR family directed antibodies in the future.