title: The role of membrane complement regulatory proteins in cancer immunotherapy.
abstract: Anti-tumor monoclonal antibody therapy represents one of the earliest targeted therapies in clinical cancer care and has achieved great clinical promise. Complement activation mediated by anti-tumor mAbs can result in direct tumor lysis or enhancement of antibody-dependent cellular cytotoxicy. Chemotaxis of phagocytic cells by complement activation products C5a is also required for certain cancer immunotherapy such as combined beta-glucan with anti-tumor mAb therapy. However, high expression levels of membrane-bound complement regulatory proteins (mCRPs) such as CD46, CD55 and CD59 on tumors significantly limit the anti-tumor mAb therapeutic efficacy. In addition, mCRPs have been shown to directly or indirectly down-regulate adaptive T cell responses. Therefore, it is desirable to combine anti-tumor mAb therapy or tumor vaccines with the blockade of mCRPs. Such strategies so far include the utilization of neutralizing mAbs for mCRPs, small interfering RNAs or anti-sense oligos for mCRPs, and chemotherapeutic drugs or cytokines. In vitro studies have demonstrated the feasibility and efficacy of such methods, although concerns have been raised about the utilization of neutralizing mAbs in vivo due to widespread expression of mCRPs on normal cells and tissues. Strategies have been developed to address these issues and more in vivo studies are needed to further validate these combination approaches.
authors.affiliation: Tumor Immunobiology Program of the James Graham Brown Cancer Center, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA. jun.yan@louisville.edu
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Allendorf
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Ruowan
authors.initials: R
authors.lastname: Yan
authors.forename: Richard
authors.initials: R
authors.lastname: Hansen
authors.forename: Rossen
authors.initials: R
authors.lastname: Donev
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D018958:CD55 Antigens / Q000276:immunology; D018957:CD59 Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use; D003165:Complement System Proteins / Q000276:immunology / Q000502:physiology*; D005240:Feasibility Studies; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018958:CD55 Antigens; D018957:CD59 Antigens; D019496:Cancer Vaccines; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D003165:Complement System Proteins