Efalizumab, a reversible T-cell modulator for psoriasis.
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.
Shear
Neil H
NH
Sunnybrook & Women's College Health Sciences Centre, University of Toronto Medical School and Ventana Clinical Research Corp., Toronto, ON. neil.shear@sw.ca
Langley
Richard G
RG
Ho
Vincent
V
D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens; D007155:Immunologic Factors; D016169:Lymphocyte Function-Associated Antigen-1; C472181:efalizumab