Blood, 1 November 2004, Vol. 104, No. 9, pp. 2635-2642.
Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-03-1110.
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From the bench to the bedside: ways to improve rituximab efficacy
Guillaume Cartron,
Hervé Watier,
Josée Golay, and
Philippe Solal-Celigny
From the UPRES-EA Immuno-Pharmaco-Génétique des Anticorps thérapeutiques (IPGA), UPRES-EA, Université François Rabelais, Tours, France; Oncologie Médicale et Maladies du Sang; Laboratoire d'Immunologie, Centre Hospitalier Universitaire de Tours, France Laboratory of Cellular and Gene Therapy "G Lanzani," Ospedali Riuniti Bergamo, Italia; Centre Jean Bernard, Le Mans, France; and Cancéropôle Grand Ouest, France.
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. (Blood. 2004;104:2635-2642)
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