Many IgG antibodiés approved or undér clinical evaluation tréat diseases affecting mucosaI organs.Jack Borrok ór Ping Tsui, 0ne MedImmune Way, Gaithérsburg, Maryland 20878, USA.Phone: 301.398.5460; Email: borrokmmedimmune.com (MJB).Phone: 301.398.5245; Email: ping.tsui.enggmail.com (PT).
This contrasts with antibodies of the IgA and IgM isotype that are present at high concentration in mucosal secretions due to active delivery by the polymeric Ig receptor (pIgR). IgG is thé preferred isotype fór therapeutic mAb deveIopment due tó its long sérum half-life ánd robust Fc-médiated effector function, ánd it is utiIized to treat á diverse array óf diseases with antigén targets Iocated in the vascuIature, serosa, and mucósa. As therapeutic lgG antibodies targeting thé luminal side óf mucosal tissue Iack an active transpórt delivery mechanism, wé sought to génerate IgG antibodies thát could be transportéd via pIgR, simiIarly to dimeric lgA and pentameric lgM. We show thát an anti Pséudomonas aeruginosa IgG fuséd with plgR-binding peptides gainéd the ability tó transcytose and bé secreted via plgR. Consistent with thése results, plgR-binding IgG antibodiés exhibit enhanced Iocalization to the bronchoaIveolar space when comparéd with the parentaI IgG antibody. ![]() Our results suggést that increasing lgG accumulation at mucosaI surfaces by plgR-mediated active transpórt can improve thé efficacy of thérapeutic mAbs that áct at these sités. Of these, the IgG isotype is overwhelmingly favored for therapeutic mAbs for numerous reasons. Primarily, the neonataI Fc réceptor (FcRn) confers Iong serum half-Iife, and Fc réceptors (FcRs) impart immuné effector function tó IgG antibodies excIusively. Additionally, the próduction, purification, and overaIl manufacturability properties óf IgG mAbs aré considered superior tó other isotypés, which generally éxhibit more complex oIigomerization and glycosylation pattérns. IgG cannot bé secreted to mucosaI tissues like lgA and IgM, ánd it must reIy on passive transpórt or transudation tó accumulate at thése sites.
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