Monoclonal antibody anti-IgE

N. Dasovich, T.D. Sweeney, S.J. Shire, C.C. Hsn, and Y.E Maa, Effect of mannitol crystallization on the stability and aerosol performance of a spray-dried pharmaceutical protein, recombinant humanized anti-IgE monoclonal antibody. J Pharm Sci, 1998. 87(11) 1406-11. 

OTHER DRUGS IN THE TREATMENT OF ASTHMA Anti-IgE Monoclonal Antibodies... 

Fahey JV, Fleming HE, Wong HH, Liu J, et al. 1997. The effect of an anti-IgE monoclonal antibody on the early-and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med. 155 1828-1834. 

Maa et al. [3.84] used spray drying and spray freeze-drying (see Chapter 5, [5.13, 5.14]) to produce protein powders for inhalation from deoxyribonuclease (rhDNase) and anti-IgE monoclonal antibody (anti-IgE Mab) with lactose as carrier. Spray freezedrying produced light and porous protein particles with superior aerosol performance. 

Anti-IgE monoclonal antibody (omalizumab) is of benefit in highly selected patients. It is given fortnightly or monthly as a subcutaneous injection. It is licensed for use by doctors experienced in severe persistent asthma. Published evidence in severe allergic asthma is poor. Trials so far have been relatively short term. 

SFD is a combination of the two previously described drying techniques in which the microdispersed liquid particles are generated through the jet nozzle in the absence of heat, then collected and frozen in liquid nitrogen before sublimation occurs. The frozen particles are then lyophilized. SFD is used in place of SD when the protein cannot withstand the temperatures in the SD process. Preparation of SFD powders of DNase and an anti-IgE monoclonal antibody were found to be superior to those prepared by SD. ... 

Andya, J.D. Maa, Y.F. Constantino, H.R. Nguyen, P.A. Dosovich, N. Sweeny, T.D. Hsu, C.C. Shire, S.J. The effect of formulation excipients on protein stability and aerosol performance of spray-dried powders of recombinant humanized anti-IgE monoclonal antibody. Pharm. Res. 1999, 16, 350-358. 

Finally, the extremely low IgE concentration in the circulation requires very sensitive detection methods — i.e. ELISA/FEIA, RIA, or modifications of these methods. Basically, these techniques are similar to those described for the detection of autoantibodies. In the case of ELISA/FEIA, it concerns a capture technique where the IgE molecule is first captured by an anti-IgE monoclonal antibody and subsequently recognized by an enzyme/fluorochrome-conjugated anti-IgE monoclonal antibody. 

The current results with an anti-IgE monoclonal antibody in clinical trials (88-93) have provided proof that preventing binding of IgE to its high-affinity recep-... 

Liu J, Lester P, Builder S, Shire SJ. Characterization of complex formation by humanized anti-IgE monoclonal antibody and monoclonal human IgE. Biochemistry... 

Baniyash M, Kehry M, Esshar Z. Anti-IgE monoclonal antibodies directed at the Pee receptor binding site. Mol Immunol 1988 25 705-711. 

Shields RL, Werther WR, Zioncheck K, O Connell L, Klassen T, Fendly B, Fiesta LG, Jardieu PM. Anti-IgE monoclonal antibodies that inhibit allergen-specific histamine release. Int Arch Allergy Immunol 1995 107 412-413. 

The bronchospasm that occurs immediately after aeroallergen inhalation in allergic asthmatic subjects is at least partly an IgE-mediated immediate hypersensitivity reaction (1). At least two lines of evidence support this mechanism for the early asthmatic response. Eirst, pretreatment with an anti-IgE monoclonal antibody attenuates the early phase response in asthmatic subjects (Fig. 1) (2,3). Second, analysis of bronchoalveolar lavage fluid collected immediately after air-... 

The role of IgE in the late asthmatic response has been established in human studies in which it has been shown that pretreatment of asthmatic subjects with rhuMAb-E25—a nonanaphylactogenic anti-IgE monoclonal antibody—attenuates the LAR (Fig. 1) (35). This study established a role for IgE in the LAR— a role that had been debated up to that point (60). It also provided suggestive evidence that anti-IgE treatment attenuates allergen-induced airway eosinophilia. 

Saban R, Haak-Frendscho M, Zine M, Ridgway J, Gorman C, Presta LG, Djorling D, Saban M, Jardieu P. Human FcERI-IgE and humanized anti-IgE monoclonal antibody MaEl 1 block passive sensitization of human and rhesus monkey lung. J Allergy Clin Immunol 1994 94 836-843. 

Korenaga M, Watanabe N, Tada I. Effects of anti-IgE monoclonal antibody on a primary infection of Strongyloides rani in mice. Parasitol Res 1991 77 362-363. 

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