From the bench to the bedside: ways to improve rituximab efficacy.
Rituximab (MabThera, Rituxan) is a chimeric IgG1 monoclonal antibody that specifically targets the CD20 surface antigen expressed on normal and neoplastic B-lymphoid cells. Rituximab is currently used in the treatment of both follicular and aggressive B-cell non-Hodgkin lymphomas. Despite its demonstrated clinical effectiveness, its in vivo mechanisms of action remain unknown and could differ by subtype of lymphoma. Rituximab has been shown to induce apoptosis, complement-mediated lysis, and antibody-dependent cellular cytotoxicity in vitro, and some evidence points toward an involvement of these mechanisms in vivo. Rituximab also has a delayed therapeutic effect as well as a potential "vaccinal" effect. Here, we review the current understanding of the mechanism of action of rituximab and discuss approaches that could increase its clinical activity. A better understanding of how rituximab acts in vivo should make it possible to develop new and more effective therapeutic strategies.
Cartron
Guillaume
G
UPRES-EA Immuno-Pharmaco-Génétique des Anticorps thérapeutiques, UPRES-EA, Université François Rabelais, Tours, France. cartron@med.univ-tours.fr
Watier
Hervé
H
Golay
Josée
J
Solal-Celigny
Philippe
P
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000187:drug effects / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D017452:Receptors, IgG / Q000187:drug effects / Q000502:physiology; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D017452:Receptors, IgG; D000069283:Rituximab