Introduction
Monoclonal antibodies (mAbs) have become an increasingly important class of drugs with a global market comprised of a total of 93 mAbs with marketing approval1 and cancer being their most prevalent target disease2. Significant breakthroughs made in the areas of hybridoma technology and recombinant antibody production enabled the development of highly specific mAbs. However, for most mAbs not only the antigen-binding Fab arm determines their therapeutic efficacy, but also the antibody isotype. More specifically, the Fc tail largely dictates the downstream effector functions of an antibody through its interaction with FcRs and complement and thus the subsequent activation of the immune system (fig.1, table 1 ). Therefore, the final outcome of the binding of an antibody to its target is critically dependent on the chosen isotype. Moreover, Fc- or glyco-engineering of the chosen isotype can be used to further optimise its effector functions and half-life. In this review we focus on optimal isotype selection for three mAb types receiving much clinical attention, which are according to their mechanism of action: (a) tumour antigen-targeting, (b) immune checkpoint inhibiting and (c) TNFR family targeting agonistic mAbs.