Ofatumumab: Difference between revisions
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< | <StructureSection load='3giz' size='450' side='right' scene='Ofatumumab/Ofatumumab/1' caption='Ofatumumab Fab Fragment, better known as Arzerra, ([[3giz]])'> | ||
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===Better Known as: Arzerra=== | ===Better Known as: Arzerra=== | ||
* Marketed By: Genmab & GlaxoSmithKline | * Marketed By: Genmab & GlaxoSmithKline | ||
* Major | * Major Indications: Chronic Lymphocytic [[Cancer|Leukemia]] & [[Rheumatoid Arthritis]] | ||
* Drug Class: Anti-CD20 [[Monoclonal Antibody]] | * Drug Class: Anti-CD20 [[Monoclonal Antibody]] | ||
* Date of FDA Approval (Patent Expiration): 2009 (2023) | * Date of FDA Approval (Patent Expiration): 2009 (2023) | ||
* 2010 Sales: $60 Million | * 2010 Sales: $60 Million | ||
* Importance: Recieved accelerated approval by the FDA for treatment of Chronic Lymphocytic [[Cancer|Leukemia]]. Targets a different CD20 epitope than [[Rituximab]]. This epitope is located closer to the cell membrane, which should allow for more effective complement deposition and subsequent cancerous B Cell killing. Further, Ofatumumab dissociates from its target at a slower rate compared to Rituximab. Currently being tested for efficacy in a number of phase II and III trials for B Cell Lymphoma and Rheumatoid Arthritis as well as Multiple Sclerosis.<ref>PMID 18003886</ref><ref>PMID: 20068404</ref> | * Importance: Recieved accelerated approval by the FDA for treatment of Chronic Lymphocytic [[Cancer|Leukemia]]. Targets a different CD20 epitope than [[Rituximab]]. This epitope is located closer to the cell membrane, which should allow for more effective complement deposition and subsequent cancerous B-Cell killing. Numerous studies validated this increased cytotoxicity. Further, Ofatumumab dissociates from its target at a slower rate compared to Rituximab. Currently being tested for efficacy in a number of phase II and III trials for B-Cell Lymphoma and Rheumatoid Arthritis as well as Multiple Sclerosis.<ref>PMID 18003886</ref><ref>PMID: 20068404</ref> | ||
* 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=== | ||
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> | 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> 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> | ||
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===References=== | ===References=== | ||
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