Complement function in mAb-mediated cancer immunotherapy

• Published in: Trends in immunology 2004-03, Vol.25 (3), p.158-164
• Main Authors: Gelderman, Kyra A., Tomlinson, Stephen, Ross, Gordon D., Gorter, Arko
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Adjuvants, Immunologic - therapeutic use; Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibody-Dependent Cell Cytotoxicity; beta-Glucans; Complement Activation - drug effects; Complement C3b - physiology; Complement Membrane Attack Complex - physiology; Complement System Proteins - physiology; Cytotoxicity, Immunologic - drug effects; Drug Design; Glucans - pharmacology; Glucans - therapeutic use; Humans; Immunotherapy; Macrophage-1 Antigen - immunology; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - physiology; Mice; Models, Immunological; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - physiology; Neoplasms - immunology; Neoplasms - therapy; Neoplasms, Experimental - immunology; Neoplasms, Experimental - therapy
• ISSN: 1471-4906; 1471-4981
• DOI: 10.1016/j.it.2004.01.008

Complement activation by mAbs can cause direct tumor cell lysis or enhance antibody-dependent cell-mediated cytotoxicity. However, tumor cells are protected from complement-mediated injury by membrane-bound complement regulatory proteins (mCRP) that are often expressed at elevated levels on tumor cells. Recent studies indicate that blocking or overwhelming the function of tumor cell mCRP might substantially improve the efficacy of monoclonal antibody (mAb) immunotherapy. In addition, the use of β-glucan as an adjuvant for mAb immunotherapy enables iC3b deposited on tumor cells by mAbs to activate complement receptor 3 (CR3) on effector cells, thus inducing CR3-dependent cellular cytotoxicity. These strategies provide novel cell-mediated mechanisms of tumor cytotoxicity that are additive to all other mAb effector mechanisms.