Anti-Factor D Reduces Inflammation

Applied Genetics News,  August, 2001  

• E-mail
• Print
• Link

Tanox, Inc. (10301 Stella Link, Suite 110, Houston TX, 77025-5497; Tel: 713/664-2288, Fax: 713/664-8914; Website: www.tanox.com) with its collaborators at Baylor, Texas, Children's Hospital, and the Texas Heart Institute (Houston, TX) reported positive results in using TNX-224, its antifactor D monoclonal antibody, to reduce inflammatory responses in an experimental model of cardiopulmonary bypass. The study appears in the July issue of the Journal of Thoracic and Cardiovascular Surgery.

TNX-224 is a monoclonal antibody specific for factor D, an element of the alternative complement pathway. In the recent study, TNX- 224 (previously known as 166-32) effectively inhibited the activation of complement, neutrophils, and platelets. The data suggest that inhibition of complement activation by TNX-224 could be useful in reducing systemic inflammation in patients undergoing cardiopulmonary bypass.

In the study, TNX-224 was added to freshly collected blood from five healthy donors and recirculated through a pediatric cardiopulmonary bypass circuit, to mimic the condition of open- heart surgery procedures. An irrelevant monoclonal antibody was used as a negative control with the same donor blood in a parallel bypass circuit on the same day. Blood samples were collected at different time points during recirculation for measurement of activation of complement, neutrophils, and platelets.

TNX-224 effectively inhibited complement activation and blocked the production of the products Bb, C3a, sC5b-9, and C5a. Up- regulation of adhesion molecules CD11b on neutrophils and CD62P on platelets was also significantly inhibited by TNX-224, which is consistent with the inhibition of the release of neutrophil- specific myeloperoxidase, elastase and platelet-specific thrombospondin. The antibody also suppressed production of the proinflammatory cytokine interleukin 8. The results suggest that inhibition of complement activation by targeting factor D during cardiopulmonary bypass procedures could prevent the inflammatory responses caused by neutrophils, platelets, and cytokines.

"Factor D may prove to be a valuable target in blocking complement-induced systemic inflammation," says Nancy Chang, president and CEO of Tanox. "TNX-224 may be useful in preventing inflammation and tissue damage during open-heart surgery involving cardiopulmonary bypass."

COPYRIGHT 2001 Business Communications Company, Inc.
COPYRIGHT 2001 Gale Group