Rituximab
From Proteopedia
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| - | < | + | <StructureSection load='2osl' size='450' side='right' scene='Rituximab/Rituximab/2' caption='Rituximab, better known as Rituxan, ([[2osl]])'> |
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===Better Known as: Rituxan=== | ===Better Known as: Rituxan=== | ||
* Marketed By: Biogen Idec, Genentech & Roche | * Marketed By: Biogen Idec, Genentech & Roche | ||
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* Date of FDA Approval (Patent Expiration): 1997 (2015) | * Date of FDA Approval (Patent Expiration): 1997 (2015) | ||
* 2009 Sales: $5.7 Billion | * 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. | + | * 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. | * See [[Pharmaceutical Drugs]] for more information about other drugs and diseases. | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
| - | Chronic Lymphocytic [[Cancer|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.<ref>doi:10.1016/j.it.2006.07.005</ref> 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. | + | Chronic Lymphocytic [[Cancer|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.<ref>doi:10.1016/j.it.2006.07.005</ref> 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.<ref>PMID: 15564720</ref> 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.<ref>PMID 20068404</ref> Rituximab is an anti-CD20 chimeric monoclonal antibody which <scene name='Rituximab/Epi/3'>binds its target epitope</scene> with exceptional specificity. Numerous studies have indicated that <scene name='Rituximab/Crt/1'>residues Ala 170 and Pro 172</scene> on human CD20 are critical determinants for effective binding. <scene name='Rituximab/All/2'>Several other interactions</scene> effectively fine tune and strengthen the bond between Rituximab and the epitope peptide.<ref>DOI 10.1074/jbc.M701654200</ref> See also [[UMass Chem 423 Student Projects 2011-2#Rituximab Fab|Rituximab Fab (UMass Chem 423 Student Projects 2011-2)]]. |
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===References=== | ===References=== | ||
<references/> | <references/> | ||
__NOEDITSECTION__ | __NOEDITSECTION__ | ||
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Current revision
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References
- ↑ 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
- ↑ 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
- ↑ Zhang B. Ofatumumab. MAbs. 2009 Jul-Aug;1(4):326-31. Epub 2009 Jul 1. PMID:20068404
- ↑ 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
