Complement and cellular cytotoxicity in antibody therapy of cancer.
The effective and practical use of mAbs in cancer therapy became a reality with the development of the chimeric anti-CD20 mAb, rituximab. Several additional mAbs have since been approved for clinical use. Despite these successes, the mechanisms by which mAbs mediate antitumor activity are still unclear. Preclinical studies indicate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) both can contribute to mAb-induced tumor cell lysis. However, evidence related to the relative clinical importance of each mechanism, and whether they are synergistic or antagonistic, is conflicting. New ways to enhance both CDC and ADCC are being developed in attempt to develop a more effective anticancer mAb. Continued research on the mechanisms of mAb therapy will be necessary if we are to take optimal advantage of the current mAbs and develop more effective mAbs in the future.
Wang
Siao-Yi
SY
University of Iowa, 5970 JPP, 200 Hawkins Drive, Iowa City, Iowa 52242, USA.
Weiner
George
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D018958:CD55 Antigens / Q000187:drug effects; D018957:CD59 Antigens / Q000187:drug effects; D003171:Complement Pathway, Classical; D003602:Cytotoxicity, Immunologic; D015195:Drug Design; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D051916:Membrane Cofactor Protein / Q000037:antagonists & inhibitors; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D000069283:Rituximab; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D007132:Immunoglobulin Isotypes; D051916:Membrane Cofactor Protein; C051590:CD59 protein, human; D000069283:Rituximab