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.