LFA-1 (CD11a) as a therapeutic target.
Leukocyte function associated antigen-1 (LFA-1) was one of the earliest of cell-surface molecules identified by monoclonal antibodies generated against leukocyte immunogens. This integrin heterodimer is perhaps best known as a classic adhesion molecule facilitating the interaction between T cells and antigen-presenting cells. However, varied studies indicate that LFA-1 has multi-faceted roles in the immune response including adhesion, activation and trafficking of leukocyte populations. While there has been long-standing interest in LFA-1 as a therapeutic target for regulating immunity, anti-LFA-1 therapy is still not a first-line indication for any clinical condition. Antagonism of LFA-1 with monoclonal antibodies, either alone or in combination with other agents, can result in regulatory tolerance in vivo. Furthermore, new generation humanized anti-LFA-1 monoclonal antibodies (Efalizumab) show at least modest promise for continued application in clinical trials. Thus, anti-LFA-1 forms a potential, but still largely unexploited, immunotherapy which may find its greatest application as an agent which augments other therapies.
Nicolls
M R
MR
Department of Medicine, University of Colorado Health Science Center, Denver, Colorado, USA. Mark.nicolls@uchsc.edu
Gill
R G
RG
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen / Q000187:drug effects* / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D036904:Leukocyte Rolling / Q000187:drug effects / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects* / Q000276:immunology; D016377:Organ Transplantation
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen; D016169:Lymphocyte Function-Associated Antigen-1; C472181:efalizumab