LFA-1 (CD11a) as a Therapeutic Target

Authors

  • M.R. Nicolls,

    Corresponding author
    1. Departments of Medicine and Immunology, University of Colorado Health Science Center, Denver, Colorado, USA
    2. Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Science Center, Denver, Colorado, USA
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  • R.G. Gill

    1. Departments of Medicine and Immunology, University of Colorado Health Science Center, Denver, Colorado, USA
    2. Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver, Colorado, USA
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*Corresponding author: Mark R. Nicolls, Mark.nicolls@uchsc.edu

Abstract

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.

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