Anti-adhesion antibodies efalizumab, a humanized anti-CD11a monoclonal antibody

Abstract

The acquired immune response that leads to graft rejection depends on regulated adhesive interactions between T lymphocytes, endothelial cells, dendritic cells, graft tissue and the extracellular matrix to coordinate cellular trafficking and activation of antigen-reactive T lymphocytes. Inhibiting the function of molecules involved in the adhesion processes offers the potential for interfering with the allograft response. The leukocyte function associated antigen-1 molecule (LFA-1), a heterodimer of CD11a (alphaL) and CD18 (beta2) integrin subunits, is an attractive therapeutic target because it plays an important role in key steps of inflammation and tissue rejection. These include: (1) binding of leukocytes to endothelium; (2) trafficking through activated endothelium; and (3) costimulatory interactions between T lymphocytes and antigen presenting cells. Clinical experience with efalizumab, a humanized anti-CD11a monoclonal antibody (mAb), in patients with chronic plaque psoriasis has shown that anti-CD11a therapy is well tolerated and effective at reducing the severity of the disease without depleting lymphocytes. Initial results in renal transplant patients are also promising.