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PBMCs Used to Generate Humanized Mice to Study Asthma

Mar 17, 2014 6:24:09 AM / by Maria

Independent publication uses peripheral blood mononuclear cells (PBMCs) supplied by HemaCare to explore the effects of IgE sequestration in a humanized mouse model of immunoglobulin production

Asthma is a common ailment whose symptoms include coughing, wheezing, shortness of breath and tightening of the chest.  In around 90% of kids and 50% of adults with asthma, the condition is attributed to allergies, wherein the immune system of the patient goes overboard to destroy harmless allergens e.g., pollen or cat dander.  Specifically, IgE antibodies are mass produced by cells such as the PBMCs (peripheral blood mononuclear cells).  IgE in turn binds to its receptors to trigger a series of reactions including histamine release to result in inflammation of respiratory airways.

Sequesteration of IgE by anti-IgE antibodies to prevent IgE binding to its high affinity receptor,  FcεRI, on PBMCs such as basophils and mast cells has been proven to be an effective therapy in previous studies. Omalizumab is one such humanized anti- IgE antibody which has shown suppression of histamine release. However, omalizumab does not suppress either the differentiation of IgE producing B cells (a specific type of PBMCs) or the continuous production of allergen-specific IgE. Rather, circulating IgE levels show sustained increase for several months after omalizumab treatment. Seung et al., in their recent paper have generated a recombinant anti-IgE antibody which can both sequester IgE and suppress the differentiation of IgE producing B cells.

For this dual pronged approach, Seung et al., engineered an antibody by targeting another

Human PBMCs in mice Human PBMCs engrafted in mice to study effect of XmAb7195 Image creditsL www.csmonitor.com

receptor, FcγRIIb. FcγRIIb is an IgG Fc receptor that inhibits B-cell receptor signaling.  They started with a murine anti-IgE antibody as a template, modified residues to humanize it, increased affinity for IgE binding, and also increased affinity for FcγRIIb.  This antibody therefore coengages FcγRIIb and IgE B-cell receptor. Comparison of effects of this antibody (XmAb7195) versus omalizumab revealed a 5-fold higher affinity for IgE and more than 400-fold affinity for FcγRIIb.  XmAb7195 suppressed the secretion of IgE both in human PBMC cultures from HemaCare and in PBMC-engrafted severe combined immunodeficiency mice.  Thus, this humanized therapeutic antibody with dual action against IgE action offers long-term management of allergic asthma.

We are excited to read how PBMCs supplied by HemaCare has helped in generation of humanized mouse to evaluate effects of IgE sequesteration in therapy for asthma. Read more about their findings and access the full article from our publication's page. Try HemaCare’s PBMCs and other blood products, which are collected in HemaCare's FDA-registered collection centers from IRB consented healthy human volunteer donors by leukapheresis.

Reference:

1.  Seung Y. Chu, Holly M. Horton, Erik Pong, Irene W. L. Leung, Hsing Chen, Duc-Hanh Nguyen, Cristina Bautista, Umesh S. Muchhal, Matthew J. Bernett, Gregory L. Moore, David E. Szymkowski, John R. Desjarlais. Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcgRIIb with Fc-engineered antibody. J. Allergy Clin. Immunol. (2012) 129 (4):1102-15. doi.org/10.1016/j.jaci.2011.11.029

 

Topics: antibodies, drug development, Independent validation, PBMCs

Maria

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