Insights into how lymphoma drugs work
Development of the anti-CD20 antibody, rituximab, heralded the start of monoclonal antibody (mAb) therapy as an effective means of treating blood cancers. Despite this undoubted impact, patient responses to treatment remain variable and require improvement. Work from our group and others indicate that a specific set of molecules called Fc receptors (FcR) expressed on the cells of the patient's immune system and the lymphoma itself regulate these responses. To make further progress we need alternative approaches based upon a better understanding of these receptors. This programme will draw upon our previous work on the mechanisms of antibody action and will study several large clinical trials using mAb, to reveal key aspects of FcR biology linked to antibody efficacy, define new prognostic markers associated with clinical response, identify safe and effective means to manipulate FcR and thereby provide a pipeline for the rational selection of new therapies to be explored clinically. The work will take as its starting point CD20 antibodies in lymphoma but will also provide mechanistic understanding that will benefit treatment with other mAb specificities and other blood cancers.