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Anti-adhesion antibodies efalizumab, a humanized anti-CD11a monoclonal antibody
Russell L Dedrick1, Patricia Walicke, Marvin Garovoy
1XOMA LLC, Berkeley, CA 94710, USA. dedrick@xoma.com
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.
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.