Overcoming Resistance to Therapeutic Antibodies by Targeting Fc Receptors

Monoclonal antibodies (mAb) are now at the forefront of cancer therapy. Their mechanisms of action remain the focus of intense investigation as it offers the prospect of increased potency through antibody engineering or adjuvant therapy. Although roles for complement and the induction of direct cell death remain controversial, the importance of Fc gamma receptors (FcγR) to the efficacy of therapeutic antibodies is irrefutable. However, the biology of these receptors is complex and it is now clear that in certain instances inappropriate expression or upregulation of FcγR can be detrimental. This complexity is compounded by recent exciting data showing that FcγR on both the effector and the target cell help govern therapeutic potency. In this review the ability of FcγR to elicit and modulate antibody therapy will be discussed alongside potential strategies to overcome the associated resistance.