søndag den 26. august 2012

Ofatumumab (Arzerra) for B-cells related disease

Rituximab (Rituxan, MabThera) is a chimeric monoclonal antibody against the CD20 molecule found on the surface of B cells.

Ofatumumab (Arzerra) is a human monoclonal antibody which targets an epitope in the CD20 molecule.

It is called a chimeric monoclonal antibody because the metod used to produce the antibody yields an animal. When mice is used for this purpose, these murine monoclonal antibodies can, when injected into humans, provoke an adverse reaction.

Therefore scientists are trying to develop fully human monoclonal antibodies to avoid side effects from the chimeric antibodies. More about monoclonal antibodies.

Ofatumumab was developed by Genmab. It is a biotechnology company, founded in Denmark in 1999. The company is specializing in the creation and development of differentiated human antibody therapeutics. Ofatumumab is being investigated for use in oncology and autoimmune diseases. More information here

Genmab uses patented UltiMAb® transgenic mouse technology to produce monoclonal human antibodies. More information here.

GlaxoSmithKline about Ofatumumab:
The binding of ofatumumab to the membrane-proximal epitope of the CD20 molecule induces recruitment and activation of the complement pathway at the cell surface, leading to complement-dependent cytotoxicity and resultant lysis of tumour cells.  Ofatumumab has been shown to induce appreciable lysis of cells with high expression levels of complement defence molecules.  Ofatumumab has also been shown to induce cell lysis in both high and low CD20 expressing cells and in rituximab-resistant cells.  In addition, the binding of ofatumumab allows the recruitment of natural killer cells allowing the induction of cell death through antibody-dependent cell-mediated cytotoxicity.

An article on Ofatumumab from 2009 informs: 
A number of anti-CD20 mAbs are under development or are already on the market. Compared to the marketed product anti-CD20 product rituximab, ofatumumab has demonstrated greater cytotoxic potential in killing B-cells though CDC (complement-dependent cytotoxicity) pathways. Thus, ofatumumab may offer alternative therapy for patients who are resistant to rituximab. Other anti-CD20 mAbs are in clinical development, including afutuzumab (Hoffmann-LaRoche/Biogen Idec), veltuzumab (Immuomedics) and ocrelizumab (Genentech/Biogen Idec). These candidates have also shown positive results in clinical trials, and are expected to enrich the pipeline of mAb therapy for B-cells related disease.

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