Ofatumumab

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<applet load="" size="480" color="" frame="true" spin="on" Scene ="Ofatumumab/Ofatumumab/1" align="right" caption="Ofatumumab Fab Fragment, better known as Arzerra, ([[3giz]])"/>
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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
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===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.<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>
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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</StructureSection>
===References===
===References===
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Current revision

Ofatumumab Fab Fragment, better known as Arzerra, (3giz)

Drag the structure with the mouse to rotate

References

  1. ↑ Coiffier B, Lepretre S, Pedersen LM, Gadeberg O, Fredriksen H, van Oers MH, Wooldridge J, Kloczko J, Holowiecki J, Hellmann A, Walewski J, Flensburg M, Petersen J, Robak T. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study. Blood. 2008 Feb 1;111(3):1094-100. Epub 2007 Nov 14. PMID:18003886 doi:10.1182/blood-2007-09-111781
  2. ↑ Zhang B. Ofatumumab. MAbs. 2009 Jul-Aug;1(4):326-31. Epub 2009 Jul 1. PMID:20068404
  3. ↑ 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
  4. ↑ 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
  5. ↑ Zhang B. Ofatumumab. MAbs. 2009 Jul-Aug;1(4):326-31. Epub 2009 Jul 1. PMID:20068404
  6. ↑ Teeling JL, Mackus WJ, Wiegman LJ, van den Brakel JH, Beers SA, French RR, van Meerten T, Ebeling S, Vink T, Slootstra JW, Parren PW, Glennie MJ, van de Winkel JG. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol. 2006 Jul 1;177(1):362-71. PMID:16785532

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David Canner, Joel L. Sussman

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