Antibodies anti-IgE

Allergy. Figure 6 Anti IgE antibodies prevent IgE from binding to their receptors on mast cells, and thus from releasing allergic mediators. 

Omalizumab is a recombinant humanized monoclonal anti-IgE antibody that inhibits binding of IgE to receptors on mast cells and basophils, resulting in the inhibition of mediator release and attenuation of the early- and late-phase allergic response. It may be a treatment option for moderate to severe persistent asthmatics 12 years of age or older whose asthma is not controlled by inhaled corticosteroids and who have a positive skin test or in vitro reactivity to perennial allergens.37 Omalizumab significantly decreases inhaled corticosteroid use, number and length of exacerbations, and increases asthma-related quality of life.37... 

Omalizumab (Xolair) is an anti-IgE antibody approved for the treatment of allergic asthma not well controlled by oral or inhaled corticosteroids. The dosage is determined by the patient s baseline total serum IgE (international units/mL) and body weight (kg). Doses range from 150 to 375 mg given subcutaneously at either 2- or 4-week intervals. 

Defining the biochemical mechanisms that couple stimulation at the cell surface to secretion by exocytosis is a major focus in biological research. In the mast cell, the steps by which immunologic secretagogues (for example, specific antigen, anti-IgE antibodies) activate a secretory response have been extensively studied and there are several reviews covering this area [ 12-14, 16, 121, 177],... 

Hamilton RG, Lichtenstein LM Down-regulation of FceRI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 1997 158 ... 

This chapter presents the basic pharmacology of the methylxanthines, cromolyn, leukotriene pathway inhibitors, and monoclonal anti-IgE antibody—agents whose medical use is almost exclusively for pulmonary disease. The other classes of drugs previously... 

Treatment with omalizumab, the monoclonal humanized anti-IgE antibody, is reserved for patients with chronic severe asthma inadequately controlled by high-dose inhaled corticosteroid plus long-acting B-agonist combination treatment (eg, fluticasone 500 meg plus salmeterol 50 meg inhaled twice daily). This treatment reduces lymphocytic, eosinophilic bronchial inflammation and effectively reduces the frequency and severity of exacerbations. It is reserved for patients with demonstrated IgE-mediated sensitivity (by positive skin test or radioallergosorbent test [RAST] to common allergens) and an IgE level within a range that can be reduced sufficiently by twice-weekly subcutaneous injections. 

Immunosuppressive therapy is utilized in chronic severe asthma, where cyclosporine is often effective and sirolimus is another alternative. Omalizumab (anti-IgE antibody) has recently been approved for the treatment of severe asthma (see previous section). Tacrolimus is currently under clinical investigation for the management of autoimmune chronic active hepatitis and of multiple sclerosis, where IFN-3 has a definitive role. 

Genentech and Novartis submit application foi FDA approval of anti-IgE antibody. 

Barnes PJ. 1999. Anti-IgE antibody therapy for asthma. NEJM. 341 2006-2008. 

Boulet LP, Chapman KR, Cote J, Kalra S, et al. 1997. Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med. 155 1835-1840. 

Busse WW, Fahy JV, Rick RB. 1998. A pilot study of the effects of an anti-IgE antibody (E25) on airway inflammation in moderate-severe asthma. Am J Respir Crit Care Med. 157 456A. 

Corren J, Diaz-Sanchez D, Reimann J,, Saxon A, Adelman D. 1998. Effects of anti-IgE antibody therapy on nasal reactivity to allergen and IgE synthesis in vivo. J All Clin Immunol. 101 S105. 

As reflected in another chapter of this volume, especially anti-inflammatory treatment by antihistamines, antileukotrienes or corticoids might influence the success of immunotherapies, because it normalizes and standardizes the immunological base of treatment [13]. In severe cases a reduction of IgE levels by anti-IgE antibodies or even a slight general immunosuppressive treatment may also be considerable [14],... 

Spray freeze drying also has been proposed as an alternative technology to produce light and porous particles for peptide and protein delivery. Liquid nitrogen is used as recipient agent, into which the formulation is sprayed. The formed microparticles are harvested and lyophilized eventually. DNase and monoclonal anti-IgE antibodies have been used to demonstrate the feasibility of this concept (Maa et al. 1999). Promaxx microspheres are manufactured in a phase-separation process between water-soluble polymers and therapeutically active protein that results in particles having a high protein payload of up to 90 percent (Brown et al. 1999). 

J.D. Reimann, R.K. Bush, M.L. Watrous, and W.J. Metzger. 1999. Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group. 

Ruffin, C.G. and B.E. Busch. 2004. Oma-lizumab a recombinant humanized anti-IgE antibody for allergic asthma. Am.]. Health Syst. Pharm. 61 1449-1459. 

Labelled anti-IgE antibody Serum IgE antibody A ergen... 

Coyle, A. J., Wagner, K Bertrand, C Tsuyuki, S Bews, J., and Heusser, C. (1996) Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production inhibition by a non-anaphy-lactogenic anti-IgE antibody. J. Exp. Med. 183, 1303-1310. 

Soler M, Matz J, Townley R, Buhl R, O Brien J, Fox H, et al. The anti-IgE antibody omaUzumab reduces exacerbations... 

The radioallergosorbent test (RAST) is a solid-phase sandwich RIA and does not suffer from these general disadvantages that is, it is a direct assay, eliminates nonspecific serum effects, and measures biologically active allergen-specific IgE sandwiched between allergen and Fc-specific anti-IgE antibodies. 

Berger W, Gupta N, McAlary M, Fowler-Taylor A. Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma. Ann Allergy Asthma limnunol 2003 91(2) 182-8. 

Nayak A, Casale T, Miller SD, Condemi J, McAlary M, Fowler-Taylor A, Della Cioppa G, Gupta N. Tolerability of retreatment with omalizumab, a recombinant humanized monoclonal anti-IgE antibody, during a second ragweed pollen season in patients with seasonal allergic rhinitis. Allergy Asthma Proc 2003 24(5) 323-9. 

Omalizumab is the first anti-IgE antibody approved for the treatment of asthma not well controlled on high doses of ICSs. Omalizumab is a composite of 95% human and 5% antihuman murine IgE sequences. The mouse protein becomes part of the receptor complex and thus is shielded from exposure to the immune system and presents a low risk for an anaphylactic response. ... 

Protein Fv binds specifically to the VH domain of immunoglobulins [22], Consequently, this endogenous protein is similar to multivalent antigens or to divalent anti-IgE antibodies. To evaluate the mechanism whereby this protein activates basophils, we incubated protein Fv with human monoclonal IgM from diverse VH families [19,29], Preincubation of basophils with three preparations of human monoclonal IgM VH3+ concentration-dependently inhibited the histamine-releasing activity of protein Fv. In contrast, a monoclonal IgM that has a Vh6 domain had no such effect. These results are compatible with the hypothesis that protein Fv binds to IgE VH3 + bound to FceRI+ cells. 

---