title: New perspectives on complement mediated immunotherapy.
abstract: Tumor-specific monoclonal antibodies (mAbs) offer several modes of tumor cell killing, from direct cytotoxic activity to indirect mechanisms employing the host immune system, particularly its innate branch. The latter effector functions seem to dominate among clinically approved anti-cancer mAbs and major efforts are being undertaken by both academia and the pharmaceutical industry with the aim to improve complement activation, antibody-dependent cellular cytotoxicity (ADCC) and Fc/opsonin-mediated phagocytosis. On one hand, there are a variety of available effector mechanisms to allow multistep elimination of tumor cells. On the other hand, tumor cells adopt a number of strategies to evade immune attack, such as overexpression of complement inhibitors, trogocytosis, shedding or internalization of mAb-targeted epitopes, which all contribute to their resistance against host defense mechanisms. Another problem recognized only recently is the depletion of immune effectors during the first round of treatment, which in concordance with delayed turnover of immune components renders subsequent rounds of therapy ineffective. Herein, we discuss newly identified limiting factors but also novel mechanistic data on complement activation by antitumor antibodies as issues important for guidance towards the next generations of immunotherapeutics.
authors.affiliation: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdańsk, Dębinki 1 Street, 80210 Gdańsk, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Stasiłojć
authors.affiliation: Department of Hematology, Karolinska University Hospital Solna, 17176 Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Österborg
authors.affiliation: Department of Translational Medicine, Lund University, The Wallenberg Laboratory, Inga Maria Nilssons Street 53, 20502 Malmö, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.affiliation: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdańsk, Dębinki 1 Street, 80210 Gdańsk, Poland. Electronic address: marcin.okroj@gumed.edu.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Okrój
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal
keywords: CD20; Complement system; Immunotherapy