Rituximab: Difference between revisions

Revision as of 12:03, 14 December 2010

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 cancer drug in the world. It was the first monoclonal antibody to be approved by the FDA which selectively targets CD20 on B-cells.
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.^[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.

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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

David Canner, Joel L. Sussman, Alexander Berchansky

[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

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 ===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.<ref>PMID: 15564720</ref> A number of studies have demonstrated that the bind 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> Ofatumumab is an anti-CD20 human monoclonal antibody which binds a unique epitope on CD20 with high specificity. This epitope is membrane proximal compared to the epitope of [[Rituximab]], which might explain Ofatumumab's increased potency compared to that of Rituximab. Further, because the epitope of Ofatumumab includes a small extracellular loop of CD20 and binds very tightly resulting in a slow off-rate, this too may explain Ofatumumab's increased CDC potency.<ref>PMID:16785532</ref>
+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.<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.
 ===References===