Summary and conclusion
A summary of the properties of CGP 51901 is shown in Table 3. On the basis of its binding to IgE and IgE-secreting cells and its activity in vitro and in vivo, CGP 51901 is expected to be able to decrease serum IgE by direct clearance of IgE and by reduction of the numbers and productivity of IgE-secreting cells. The end result of reduction of IgE in the circulation and on mast cells is expected to be the attenuation of IgE-mediated reactions and the improvement in allergy symptoms. The effective serum concentration of CGP 51901 is expected to be in the range 1–10 μg/ml. Because CGP 51901 is an antibody specific for IgE, it is expected to be highly selective in its activity. Because IgE does not appear to be essential and because CGP 51901 has been rigorously tested to confirm its non-anaphylactic nature, this treatment is not expected to have any adverse effects. Therefore, CGP 51901 is expected to be safe and to have a good probability of being effective when it is tested in human clinical trials.
Similar content being viewed by others
References
Beatty JD, Beatty BG, Vlahos WG (1987) Measurement of monoclonal antibody affinity by non-competitive enzyme immunoassay. J Immunol Methods 100:173
Bergstedt-Lindqvist S, Moon H-B, Persson U, Müller G, Heusser C, Severinson E (1988) Interleukin 4 instructs uncommitted B lymphocytes to switch to IgG1 and IgE. Eur J Immunol 18:1073
Brüggemann M, Williams GT, Bindon CI, Clark MR, Walker MR, Jefferis R, Waldmann H, Neuberger MS (1987) Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med 166:1351
Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG (1989) Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 320:271
Chang TW (1990) Monoclonal antibodies specific for IgE-secreting B lymphocytes. ICSU Short Reports 10:188
Chang TW, Davis FM, Sun NC, Sun CRY, MacGlashan DW Jr, Hamilton RG (1990) Monoclonal antibodies specific for human IgE-producing B cells: a potential therapeutic for IgE-mediated allergic diseases. Bio/Technology 8:122
Coffman RL, Carty J (1986) A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-γ. J Immunol 136:949
Davis FM, Gossett LA, Chang TW (1991) An epitope on membrane-bound but not secreted IgE: implications in isotype-specific regulation. Bio/Technology 9:53
Delespesse G, Sarfati M, Hofstetter H (1989) Human IgE-binding factors. Immunol Today 10:159
Eisen HN (1980) Antibody-mediated (immediate-type) hypersensitivity. In: Davis BD, Dulbecco R, Eisen HN, Ginsberg HS (eds) Microbiology. Harper & Row, Philadelphia, pp 468–492
Finkelman FD, Katona LM, Urban JF Jr, Snapper CM, Ohara J, Paul WE (1986) Suppression of in vivo polyclonal IgE response by monoclonal antibody to the lymphocyte B cell stimulatory factor-1. Proc Natl Acad Sci USA 83:9675
Finkelman FD, Holmes J, Katona IM, Urban JF Jr, Bechman MP, Park LS, Schooley KA, Coffman RL, Mosmann TR, Paul WE (1990) Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol 8:303
Frick OL (1987) Immediate hypersensitivity. In: Sites DP, Stobo JD, Wells JV (eds) Basic and clinical immunology, 6th edn. Appleton and Lange, Norwalk, pp 197–227
Gillespie E, Lichtenstein LM (1972) Histamine release from human leukocytes: studies with deuterium oxide, colchicine and cytochalasin B. J Clin Invest 51:2941
Gordon J, Flores-Romo L, Cairns JA, Millsum MJ, Lane PJ, Johnson GD, MacLennon ICM (1989) CD23: a multifunctional receptor/lymphokine? Immunol Today 10:153
Haba S, Nisonoff A (1990) Inhibition of IgE synthesis by anti-IgE: role in long-term inhibition of IgE synthesis by neonatally administered soluble IgE. Proc Natl Acad Sci USA 87:3363
Heusser ChH, Bews J, Brinkmann V, Delespesse G, Kilchherr E, Ledermann F, LeGros G, Wagner K (1991) New concepts of IgE regulation. Int Arch Allergy Appl Immunol 94:1
Ishida N, Ueda S, Hayashida H, Miyata T, Honjo T (1982) The nucleotide sequence of the mouse immunoglobulin epsilon gene: comparison with the human epsilon gene sequence. EMBO J 1:1117
Ishizaka K (1988) IgE-binding factors and regulation of the IgE antibody response. Annu Rev Immunol 6:513
Ishizaka K, Ishizaka T (1989) Allergy. In: Paul WE (ed) Fundamental Immunology, 2nd edn. Raven Press, New York, pp 867–888
Ishizaka T, Ishizaka K (1984) Activation of mast cells for mediator release through IgE receptors. Prog Allergy 34:188
Katona IM, Urban JF Jr, Kang SS, Paul WE, Finkelman FD (1991) IL-4 requirements for the generation of secondary in vivo IgE responses. J Immunol 146:4215
Khazaeli MB, Saleh MN, Liu TP, Meredith RF, Wheeler RH, Baker TS, King D, Seeher D, Allen L, Rogers K, Colcher D, Schlom J, Shochat D, LoBuglio AF (1991) Pharmacokinetics and immune response of 131I-chimeric mouse/human B72.3 (human gamma 4) monoclonal antibody in humans. Cancer Res 51:5461
Kuhn R, Rajewsky K, Muller W (1991) Generation and analysis of IL-4 deficient mice. Science 254:707
Levy DA, Chen J (1970) Healthy IgE-deficient person. N Engl J Med 283:541
Lichtenstein LM, Kagey-Sobotka A, White JM, Hamilton RG (1992) Anti-human IgG causes basophil histamine release by acting on IgG-IgE complexes bound to IgE receptors. J Immunol 148:3929
Liou RS, Rosen EM, Fung MSC, Sun NC, Sun C, Gordon W, Chang NT, Chang TW (1989). A chimeric mouse-human antibody that retains specificity for HIV gp120 and mediates the lysis of HIV-infected cells. J Immunol 143:3967
LoBuglio AF, Wheeler RH, Trang J, Haynes A, Rogers K, Harvey EB, Sun L, Ghrayeb J, Khazaeli MB (1989) Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. Proc Natl Acad Sci USA 86:4220
MacGlashan DW Jr, Peters SP, Warner J, Lichtenstein LM (1986) Characteristics of human basophil sulfidopeptide leukotriene release: releasability defined as the ability of the basophil to respond to dimeric cross-links. J Immunol 136:2231
Magnusson CGM, Johansson SGO (1989) Clinical significance of anti-IgE autoantibodies and immune complexes containing IgE. Clin Rev Allergy 7:73
Marshall JS, Bell EB (1985) Induction of an auto-anti-IgE response in rats. I. Effects on serum IgE concentrations. Eur J Immunol 15:272
Metzger H, Alcaraz G, Hohman R, Kinet JP, Pribluda V, Quarto R (1986) The receptor with high affinity for immunoglobulin E. Annu Rev Immunol 4:419
Moqbel R, Pritchard DI (1990) Parasites and allergy: evidence for a “cause and effect” relationship. Clin Exp Allergy 20:611
National Heart, Lung and Blood Institute (1991) National Asthma Education Program, Expert Panel Report. Guidelines for the diagnosis and management of asthma. IV. Overview of approaches to asthma therapy. J Allergy Clin Immunol 88:451
NIAID (1991) NIAID Profile Fiscal Year 1990. National Institutes of Health, Bethesda, p 77
Paul WE, Ohara J (1987) B-cell stimulatory factor-I/interleukin 4. Annu Rev Immunol 5:429
Rocklin RE, David J (1991) Immediate hypersensitivity. In: Rubenstein E, Federman DD (eds) Scientific American medicine, Scientific American, New York, pp 1–14, 33–35
Rousseaux-Prevost R, Rousseaux J, Bazin H (1987) Studies of the IgE binding site to rat mast cell receptor with proteolytic fragments and with a monoclonal antibody directed against epsilon heavy chain: evidence that the combining sites are located in the Cɛ3 domain. Mol Immunol 24:187
Sadick MD, Heinzel FP, Holaday BJ, Pu RT, Dawkins RS, Locksley RM (1990) Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon-gamma-independent mechanism. J Exp Med 171:115
Sakoyama Y, Hong KJ, Byun SM, Hisajami H, Ueda S, Yaoita Y, Hayashida H, Miyata T, Honjo T (1987) Nucleotide sequences of immunoglobulin genes of chimpanzee and orangutan: DNA molecular clock and hominid evolution. Proc Natl Acad Sci USA 84:1080
Saleh MN, Khazaeli MB, Wheeler RH, Allen L, Tilden AB, Grizzle W, Reisfeld RA, Yu AL, Gillies SD, LoBuglio AF (1992) Phase I trial of the chimeric anti-GD2 monoclonal antibody ch 14.18 in patients with malignant melanoma. Hum Antibod Hybridomas 3:19
Sears MR, Burrows B, Flannery EM, Herbison GP, Hewitt CJ, Hollaway MD (1991) Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 325:1067
Siraganian R (1988) Mast cells and basophils. In: Gallin JI, Goldstein IM, Snyderman R (eds) Inflammation: basic principles and clinical correlates. Raven Press, New York, pp 513–542
Siraganian RP, Hook WA (1980) Histamine-release and assay methods for the study of human allergy. In: Rose NR, Friedman H (eds) Manual of clinical chemistry, 2nd edn. American Society for Microbiology, Washington D.C., pp 808–821
Souillet G, Roussel F, DeVries J (1989) Alpha-interferon treatment of a patient with hyper IgE syndrome. Lancet 1:1384
Spiegelberg HL (1984) Structure and function of Fc receptors for IgE on lymphocytes, monocytes, and macrophages. Adv Immunol 35:61
Statistics of Allergy Diseases and Immunology (1992) American Academy of Allergy and Immunology, Milwaukee
Steplewski Z, Sun LK, Shearman CW, Ghrayeb J, Daddona P, Koprowski H (1988) Biological activity of human-mouse IgG1, IgG2, IgG3, and IgG4 chimeric monoclonal antibodies with antitumor specificity. Proc Natl Acad Sci USA 85:4852
Sun LK, Liou RS, Sun NC, Gossett LA, Sun C, Davis FM, MacGlashan DW Jr, Chang TW (1991) Transfectomas expressing both secreted and membrane-bound forms of chimeric IgE with anti-viral specificity. J Immunol 146:199
Thena DM, Marshall JS, Haeney MR, Bell EB (1989) A survey of nonatopic and atopic children and adults for the presence of anti-IgE autoantibodies. Clin Immunol Immunopathol 53:40
Thyphronitis G, Max EE, Finkelman FD (1991) Generation and cloning of stable human IgE-secreting cells that have rearranged the Cɛ gene. J Immunol 146:1496
Walker MR, Woof JM, Brüggemann M, Jefferis R, Burton DR (1989) Interaction of human IgG chimeric antibodies with the human FcRI and FcRII receptors: requirements for antibody-mediated host cell-target cell interaction. Mol Immunol 26:403
Winter G, Milstein C (1991) Man-made antibodies. Nature 349:293
Yelton DE (1991) Clinical experience with the L6 anti-carcinoma antibody. In: Antibody engineering. IBC USA Conferences, South Natick
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Davis, F.M., Gossett, L.A., Pinkston, K.L. et al. Can anti-IgE be used to treat allergy?. Springer Semin Immunopathol 15, 51–73 (1993). https://doi.org/10.1007/BF00204626
Issue Date:
DOI: https://doi.org/10.1007/BF00204626