Monday, 2 August 2010

Antibody therapy

Ron Levy, professor of Medicine at Stanford University, is the man who took the first steps in the development of antibodies as a therapy.1 In 1976 Dr. Levy discovered that antibodies can be made in the lab that will identify and bind to cancerous cells, triggering an immune response that destroys the cancerous cells. His initial work focused on creating tailor-made antibodies for use in individual patients, but as this would be unfeasible at an industrial level, the treatment was developed into a large-scale drug. This drug didn't target only cancer cells, but targeted all B-cells of the immune system. The results were surprising, as people did very well despite having their bodies depleted of B-cells - cells that form a significant part of the immune system. This drug is marketed under the name "Rituximab" or "Rituxan".

Rituximab works by identifying a specific protein on the outside of B-cells, called CD20.2 When Rituximab binds to CD20, the body's immune system is triggered, leading to the destruction of that B-cell. Since Rituximab doesn't distinguish between cancerous and non-cancerous B-cells, all B-cells in the body are targeted. This therapy has a number of serious potential side-effects, but is attractive to use since it doesn't cause the nausea and malaise caused by other treatments like chemotherapy. It can also be used repeatedly if relapse occurs, with improved response at each consecutive treatment.

Rituximab has been used successfully in the treatment of lupus3, rheumatoid arthritis4, and in transplants to prevent rejection of transplanted tissue.5

Since the development of Rituximab, a large amount of research has been done on the usage of antibodies to treat various cancers and diseases. As can be seen from the illustration below, antibody therapies have been developed to treat blood-related cancers (hematologic malignancies) and solid tumors, targeting a number of surface proteins on B-cells. There is an excellent review on the topic of antibody therapies, their development and application, as well as their potential use in the targeting of influenza virus here.6



1 http://stanmed.stanford.edu/2004fall/levy.html
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2Pescovitz M.D. Rituximab, an Anti-CD20 Monoclonal Antibody: History and Mechanism of Action. American Journal of Transplantation 6:859-866 (2006).
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3 Eisenberg R. SLE - Rituximab in lupus. Arthritis Res Ther. 5: 157–159 (2003).
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4 http://www.rituxan.com/ra/patient/index.xhtml
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5 Salama A. and Pusey C.D. Drug Insight: rituximab in renal disease and transplantation. Nature Clinical Practice Nephrology 2: 221-230 (2006).
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6 Guzmán F. Overview on monoclonal antibody therapy: PPT, images and videos. Pharmacology Corner http://pharmacologycorner.com/overview-on-monoclonal-antibody-therapy-ppt-images-and-videos/
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