Rituximab is a chimeric (murine/human) monoclonal IgG1κ antibody directed against the CD20 antigen (human B-lymphocyte-restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein located on pre-B and mature B lymphocytes as well as greater than 90% of B-cell non-Hodgkin’s lymphomas (NHL). CD20 is not, however, found on hematopoietic stem cells, pro-B-cells, normal plasma cells or other normal tissues. CD20 regulates early step(s) in the activation process for cell cycle initiation and differentiation, and possibly functions as a calcium ion channel.
It is appreciated that rituximab is toxic to CD20-containing B lymphocytes and lymphoma cells through various mechanisms. In vitro, once the Fab domain of rituximab binds to the CD20 antigen on B lymphocytes, the Fc domain recruits immune effector functions to mediate B-cell lysis. Possible mechanisms of cell lysis include complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Rituximab binding has also been shown to induce apoptosis in the DHL-4 human B-cell lymphoma line.
Initially designed and licensed for treatment of non-Hodgkin's lymphoma, rituximab enjoys wide use in the treatment of follicular and diffuse large B-cell NHL. More recently, clinical trials of rituximab in combination with methotrexate in the treatment of anti-TNF refractory rheumatoid arthritis demonstrated benefit, and this became a licensed indication in the US in 2006.
Serious adverse reactions associated with rituximab include fatal infusion reactions, tumor lysis syndrome, severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy.
| Source | Link | Revision Date | Access Date |
| Rituxan Prescribing Information | http://www.gene.com/gene/products/in...xan/insert.jsp | 2008-January | 2008-June-04 |
| Smolen JS, Keystone EC, et al; Working Group on the Rituximab Consensus Statement. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2007 Feb;66(2):143-50 | http://www.ncbi.nlm.nih.gov/pubmed/17068064 | 2008-June-05 | |
| Cohen SB, Emery P, et al. REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006 Sep;54(9):2793-806 | http://www3.interscience.wiley.com/c...5884/HTMLSTART | 2008-June-05 | |
| Marcus R, Hagenbeek A. The therapeutic use of rituximab in non-Hodgkin's lymphoma. Eur J Haematol Suppl. 2007 Jan;(67):5-14 | http://www.ncbi.nlm.nih.gov/pubmed/17206982 | 2008-June-05 |
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