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Rituximab

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Rituximab, better known as Rituxan, (2osl)

Better Known as: Rituxan

  • Marketed By: Biogen Idec, Genentech & Roche
  • Major Indications: B-Cell & Follicular Lymphoma, Leukemia, & Rheumatoid Arthritis
  • Drug Class: Anti-CD20 Monoclonal Antibody
  • Date of FDA Approval (Patent Expiration): 1997 (2015)
  • 2009 Sales: $5.7 Billion
  • Importance: The best selling cancer treatment in the world. It was the first monoclonal antibody to be approved by the FDA which selectively targets CD20 on B-cells. Also an effective treatment for some autoimmune diseases. Serves as the foundation upon which other, more specific and effective anti-CD20 therapies are being developed.
  • See Pharmaceutical Drugs for more information about other drugs and diseases.

Mechanism of Action

Chronic Lymphocytic Leukemia & Rheumatoid Arthritis are diseases associated with B-cell dysfunction. B-cells play a key role in the humoral immune system by acting as antigen-presenting cells (which activate T-cells) and by eventually producing antibodies against invading antigens.[1] Although the function of B-Lymphocyte Antigen CD20 has not yet been determined, and in fact knockout mice which do not produce CD20 are healthy, CD20 is expressed on almost all normal and malignant B-cells. Since it is not expressed on other plasma cells or normal tissues, it is an ideal target for passive immunotherapy.[2] A number of studies have demonstrated that the binding of monoclonal antibodies to CD20 results in recruitment of immunological devices that trigger cytotoxic events, such as compliment-dependent cytotoxicity (CDC). CDC is the major natural immune response in the body triggered by antibody binding, used to eliminate invading or dysfunctional pathogenic cells.[3] Rituximab is an anti-CD20 chimeric monoclonal antibody which with exceptional specificity. Numerous studies have indicated that on human CD20 are critical determinants for effective binding. effectively fine tune and strengthen the bond between Rituximab and the epitope peptide.[4]

References

  1. Montecino-Rodriguez E, Dorshkind K. New perspectives in B-1 B cell development and function. Trends Immunol. 2006 Sep;27(9):428-33. Epub 2006 Jul 24. PMID:16861037 doi:10.1016/j.it.2006.07.005
  2. Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2005;8:140-74. PMID:15564720 doi:10.1159/000082102
  3. Zhang B. Ofatumumab. MAbs. 2009 Jul-Aug;1(4):326-31. Epub 2009 Jul 1. PMID:20068404
  4. Du J, Wang H, Zhong C, Peng B, Zhang M, Li B, Huo S, Guo Y, Ding J. Structural basis for recognition of CD20 by therapeutic antibody Rituximab. J Biol Chem. 2007 May 18;282(20):15073-80. Epub 2007 Mar 29. PMID:17395584 doi:10.1074/jbc.M701654200


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