Inhibition of human cord blood-derived mast cell responses by anti-Fc epsilon RI mAb 15/1 versus anti-IgE Omalizumab.
Aggregation of the alpha-chain of the high affinity IgE receptor (Fc epsilon RI alpha) on mast cells or basophils after cross-linking of receptor-bound IgE by its antigen or an anti-IgE antibody results in cell activation and release of inflammatory mediators. Omalizumab (Xolair), Novartis Pharmaceuticals; Genentech Inc.) is a recombinant humanized anti-IgE mAb developed for the treatment of severe allergic asthma. It complexes with free serum IgE, which prevents its binding to Fc epsilon RI and thereby interrupts the allergic cascade. Administration of an inhibitory anti-Fc epsilon RI alpha mAb may represent an alternative strategy to neutralize IgE-mediated receptor activation. In the present report, for the first time, we have performed direct side of side comparison between the inhibitory anti-Fc epsilon RI alpha mAb designated 15/1 and Omalizumab for their effects on human cord blood-derived mast cells. We provide the first evidence that both 15/1 mAb and Omalizumab efficiently inhibit Fc epsilon RI-mediated human mast cell responses in vitro (degranulation, activation, release of IL-8 and IL-13, phosphorylation of Akt) and that mAb 15/1 is a non-anaphylactogenic antibody, which compared to Omalizumab, displays markedly higher inhibitory potency in the presence of high IgE levels.
Mirkina
Irina
I
Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1235 Vienna, Austria.
Schweighoffer
Tamás
T
Kricek
Franz
F
D000707:Anaphylaxis / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology*; D000069444:Omalizumab; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017455:Receptors, IgE / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D000069444:Omalizumab; D007073:Immunoglobulin E; D051058:Oncogene Protein v-akt