title: Regulation of complement and modulation of its activity in monoclonal antibody therapy of cancer.
abstract: The complement system is a powerful tool of the innate immune system to eradicate pathogens. Both in vitro and in vivo evidence indicates that therapeutic anti-tumor monoclonal antibodies (mAbs) can activate the complement system by the classical pathway. However, the contribution of complement to the efficacy of mAbs is still debated, mainly due to the lack of convincing data in patients. A beneficial role for complement during mAb therapy is supported by the fact that cancer cells often upregulate complement-regulatory proteins (CRPs). Polymorphisms in various CRPs were previously associated with complement-mediated disorders. In this review the role of complement in anti-tumor mAb therapy will be discussed with special emphasis on strategies aiming at modifying complement activity. In the future, clinical efficacy of mAbs with enhanced effector functions together with comprehensive analysis of polymorphisms in CRPs in mAb-treated patients will further clarify the role of complement in mAb therapy.
authors.affiliation: a Laboratory for Immunotherapy; Laboratory for Translational Immunology (LTI) ; University Medical Center Utrecht ; Utrecht , The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Meyer
authors.forename: Jeanette H W
authors.initials: JH
authors.lastname: Leusen
authors.forename: Peter
authors.initials: P
authors.lastname: Boross
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018448:Models, Immunological; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D003165:Complement System Proteins
keywords: ADCC, antibody-dependent cell-mediated cytotoxicity; CDC, complement-dependent cytotoxicity; CDCC, complement-dependent cellular cytotoxicity; CRPs, complement-regulatory proteins; antibody therapy; complement; complement-dependent cytotoxicity; complement-enhanced ADCC; tumor