Anti-CD23.
CD23, the low-affinity immunoglobulin (Ig)E receptor (FcepsilonRII), is widely distributed on the surface of various human cells. CD23 mediates numerous IgE-related immune responses (including allergen focusing) by enhancing IgE antigen complex presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells, and stimulating production of pro-inflammatory mediators from monocytes/macrophages, eosinophils, and even airway smooth muscle cells. Both membrane and soluble CD23 play an important role in allergic reactions. Cellular contacts and cytokines modulate its expression in a concerted manner as needed for allergic reactions. Expression of CD23 and soluble CD23 has been associated with allergic diseases. Targeting CD23 with monoclonal antibody (MAb) is a promising candidate therapy in allergic diseases. A newly developed agent known as Lumiliximab, which is an anti-CD23 MAb (Lumiliximab), was demonstrated to be a well-tolerated agent in a phase I clinical trial (a placebo-controlled study with allergic asthma). Adverse events were mild, and no relationship was apparent between the dose of Lumilixilab and the frequency, severity, or type of event. Sustained and dose-dependent decreases in mean serum total IgE concentrations were noted. The serum half-life of Lumilixilab increased from 2 to 10 d with increasing doses. Blocking antigen presentation, preventing costimulation signals, and reducing production of pro-inflammatory mediators are some of the potential mechanisms involved for anti-CD23 activity. Although the safety and clinical efficacy of Lumilixilab in allergic asthma and rhinitis require confirmation, the observed data imply that anti-CD23 is a promising candidate therapy option for future treatment of allergic diseases.
Rosenwasser
Lanny J
LJ
Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center/University of Colorado Health Sciences Center, Denver, CO, USA. rosenwasserl@njc.org
Meng
Jianfeng
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000188:drug therapy; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D017455:Receptors, IgE; D007073:Immunoglobulin E; C509683:lumiliximab