From the bench to the bedside: ways to improve rituximab efficacy

• Published in: Blood Vol. 104; no. 9; pp. 2635 - 2642
• Main Authors: Cartron, Guillaume, Watier, Hervé, Golay, Josée, Solal-Celigny, Philippe
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.11.2004; The Americain Society of Hematology
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20 - drug effects; Antigens, CD20 - physiology; Antineoplastic agents; Biological and medical sciences; Cytotoxicity, Immunologic - drug effects; Hematologic and hematopoietic diseases; Humans; Immunotherapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Pharmacology. Drug treatments; Receptors, IgG - drug effects; Receptors, IgG - physiology; Rituximab; Treatment Outcome; Human; Immune response; Treatment efficiency; Rituximab; Cytotoxicity; Malignant hemopathy; B-Lymphocyte; Monoclonal antibody; Malignant tumor; Non Hodgkin lymphoma; Treatment; Cell death; Lymphoproliferative syndrome; Immunotherapy; Antibody-dependent cell cytotoxicity; Anticytokine; Mechanism of action; Apoptosis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-03-1110

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)