Rituximab: mechanism of action.
Rituximab is a mainstay in the therapy for a broad variety of B-cell malignancies. Despite its undeniable therapeutic value, we still do not fully understand the mechanisms of action responsible for rituximab's anti-tumor effects. Direct signaling, complement-mediated cytotoxicity (CMC), and antibody-dependent cellular cytotoxicity (ADCC) all appear to play a role in rituximab efficacy. In vitro, animal model and clinical data addressing each of these mechanisms of action are reviewed, as are data speaking to the complexity of interactions between these mechanisms. Taken together, these data suggest different mechanisms are likely important in different scenarios. Study of the complex mechanisms of action that contribute to the clinical efficacy of rituximab have led to novel clinical trials including novel combinations, schedules, and generation of additional antibodies designed to have even greater effect. Such studies need to be accompanied by rigorous correlative analysis if we are to understand the importance of various mechanisms of action of rituximab and use that information to improve on what is already an indispensable component of therapy.
Weiner
George J
GJ
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242-1002, USA.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D018951:Antigens, CD20 / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002986:Clinical Trials as Topic; D003167:Complement Activation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D058851:GPI-Linked Proteins; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology; D021962:Membrane Microdomains / Q000187:drug effects; D051379:Mice; D017452:Receptors, IgG / Q000187:drug effects / Q000502:physiology; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D000069283:Rituximab