The clinical application of monoclonal antibodies (mAbs) revolutionised
the field of cancer therapy as it enabled the successful treatment of
previously untreatable types of cancer. Different mechanisms play a role
in the anti-tumour effect of mAbs and both target engagement with the
Fab arm as well as Fc-mediated effector functions contribute to the
efficacy of treatment. Because Ig isotypes differ in their ability to
bind to FcRs on immune cells as well as in their ability to activate
complement, they differ in the immune responses they activate.
Therefore, the choice of antibody isotype for therapeutic mAbs is
dictated by its intended mechanism of action. Considering that clinical
efficacy of many mAbs is currently achieved only in subsets of patients,
optimal isotype selection and Fc optimisation during antibody
development may represent an important step towards improved patient
outcome. Here, we discuss the current knowledge of the therapeutic
effector functions of different isotypes and Fc-engineering strategies
to improve mAbs application.