The role of complement in mAb-based therapies of cancer

The ability of complement to promote lysis of antibody-opsonized cells is well-established. Virtually all of the molecular details of this reaction have been elucidated and numerous points of regulation have also been delineated. Use of this information, along with the techniques that were first applied in the fundamental studies of complement, has allowed for investigations of the role of complement in mAb-based immunotherapies of cancer. These studies, which have often combined in vitro investigations with parallel correlative clinical measurements, have revealed that several FDA-approved mAbs make use of complement as an effector function in promoting opsonization and killing of targeted malignant cells. We describe the key methods used in this work, and discuss how the results of these studies provide rational approaches for making more effective use of complement in mAb-based cancer immunotherapy.