Magazine article Drug Topics

New Monoclonal Antibody Aims to Thwart Organ Rejection

Magazine article Drug Topics

New Monoclonal Antibody Aims to Thwart Organ Rejection

Article excerpt

Genetically engineered to be nine parts man and one part mouse, a new monoclonal antibody-indicated for prophylaxis of acute organ rejection in patients receiving renal transplants-may offer several advantages due to its humanized touch.

Manufactured by Hoffmann-La Roche Inc., Zenapax (daclizumab) is intended to be added to an immunosuppressive regimen in hopes of further reducing patients' risk of organ rejection. And while most would assume that the antibody's inclusion into an already side effect-prone therapy would produce further unwanted effects, studies suggest otherwise. The incidence of serious adverse effects reported by patients receiving immunosuppressive agents with either daclizumab or placebo was similar. Cellulitis and wound infections, however, were reported at a higher.rate in patients given a daclizumab-containing regimen.

The reason behind daclizumab's minimal toxicity profile appears to be its mostly human content. Mark Pescovitz, M.D., associate professor, department of surgery and microbiologyimmunology, Indiana University, explained that when a murine (mouse) antibody is introduced into the body, it's identified as foreign, and it triggers the immune system to produce its own antibodies to aid in clearing the intruding substance. This defensive response results in reactions, such as fever and chills. And because a murine antibody is cleared rapidly, it must be administered fairly often-once daily.

Daclizumab was developed through recombinant DNA technology, where a portion from a murine-derived monoclonal antibody was removed and reattached to a human antibody. The murine piece contains the crucial component that binds to and inhibits interleukin-2-mediated activation of lymphocytes-a critical pathway in the cellular immune response involved in allograft rejection. The end product, a humanized monoclonal antibody, is less likely to appear so unfamiliar and to trigger the immune system to produce the side effect-causing antibodies. In addition, daclizumab remains in the system longer, allowing for administration once every other week.

So how successful is the new antibody at keeping the new kidney safe and sound? Studies have demonstrated that daclizumab, in combination with other immunosuppressive agents, reduced kidney rejection episodes from 47% to 27% in one trial and from 35% to 22% in another. …

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