Efalizumab, a reversible T-cell modulator for psoriasis

Journal of Cutaneous Medicine and Surgery
N H ShearVincent Ho

Abstract

The humanized monoclonal antibody (MAb) efalizumab (Raptiva) was developed to meet a longstanding need for specific, safe, and effective anti-psoriatic treatments. Efalizumab, which is directed at the lymphocyte surface protein LFA-1, prevents multiple interactions between T cells and other cell types. Here, we review the inflammatory pathway that drives the development of psoriasis, and we discuss several mechanisms by which efalizumab suppresses skin inflammation in psoriasis. Efalizumab reversibly increases circulating T-cell counts, as T cells--including pathogenic CD8 memory T cells that are prominent in psoriatic lesions-- are specifically restrained from leaving the bloodstream and entering the skin. Within two weeks of the onset of efalizumab treatment, cell surface and intracellular LFA-1 pools are substantially cleared by lysosomal degradation. Residual surface LFA-1 molecules remain saturated with bound efalizumab for some weeks following cessation of treatment. Efalizumab's pharmacodynamic properties are consistent with its profound and reversible beneficial effects on the histopathology of psoriatic skin.

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Citations

Jul 12, 2007·Seminars in Immunopathology·Robert C Fuhlbrigge, Carsten Weishaupt
Apr 25, 2006·Journal of Cutaneous Medicine and Surgery·Yves PoulinAditya K Gupta
Apr 25, 2006·Journal of Cutaneous Medicine and Surgery·Kim A PappCatherine Zip
Apr 26, 2007·Angiogenesis·Carla CostaRaquel Soares
Jun 3, 2008·Arthritis and Rheumatism·Manuelle ViguierHervé Bachelez
Mar 21, 2009·Journal of Cutaneous Medicine and Surgery·Charles Lynde

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