Binding of cynomolgus monkey IgE to a humanized anti-human IgE antibody and human high affinity IgE receptor.
Antibodies which block IgE binding to its high affinity receptor have the therapeutic potential for treating allergic diseases. A humanized anti-human IgE antibody (E25) was developed for this purpose. Cynomolgus monkeys were used for preclinical studies of E25. We studied the binding of purified human IgE and cynomolgus monkey IgE to E25 and the human high affinity IgE receptor alpha-chain-IgG fusion molecule (Fc epsilon RI-IgG) by surface plasmon resonance. Human IgE and cynomolgus monkey IgE bound to immobilized E25 with similar affinity (apparent Kd = 0.06 and 0.19 nM, respectively). Human IgE and cynomolgus monkey IgE also bound to immobilized Fc epsilon RI-IgG with similar affinity (apparent Kd = 0.28 and 0.30 nM, respectively). These data suggest that the cynomolgus monkey is a valid model for preclinical studies of the E25 antibody and probably for other antibodies which block IgE binding to its receptor. An enzyme-linked immunosorbent assay (ELISA) for measuring cynomolgus monkey IgE was developed to support preclinical studies. This ELISA used FcERI-IgG for capture and peroxidase labelled goat polyclonal antibody to human IgE for detection. Using purified cynomolgus monkey IgE as the standard, the serum IgE levels in six cynomolgus monkeys measured were 4-23 micrograms/ml.
Meng
Y G
YG
Department of BioAnalytical Technology, Genentech Inc., South San Francisco, CA 94080, USA.
Singh
N
N
Wong
W L
WL
D000818:Animals; D000915:Antibody Affinity; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008252:Macaca fascicularis; D009194:Myeloma Proteins / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity; D014407:Tumor Cells, Cultured
D009194:Myeloma Proteins; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E