{"id":13440,"date":"2023-07-04T10:18:00","date_gmt":"2023-07-04T10:18:00","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=journal-paper&p=13440"},"modified":"2026-01-30T10:24:25","modified_gmt":"2026-01-30T10:24:25","slug":"tralokinumab-effectively-disrupts-the-il-13-il-13r%ce%b11-il-4r%ce%b1-signaling-complex-but-not-the-il-13-il-13r%ce%b12-complex","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/tralokinumab-effectively-disrupts-the-il-13-il-13r%ce%b11-il-4r%ce%b1-signaling-complex-but-not-the-il-13-il-13r%ce%b12-complex\/","title":{"rendered":"Tralokinumab Effectively Disrupts the IL-13\/IL-13R\u03b11\/IL-4R\u03b1 Signaling Complex but Not the IL-13\/IL-13R\u03b12 Complex"},"content":{"rendered":"\n

Maxim A X Tollenaere,\u00a0Christina M\u00f8lck,\u00a0Ian Henderson<\/strong>,\u00a0Scott Pollack<\/strong>,\u00a0Philip Addis<\/strong>,\u00a0Helle Heibroch Petersen,\u00a0Hanne Norsgaard<\/p>\n\n\n\n

Abstract<\/strong><\/p>\n\n\n\n

Tralokinumab, a fully human mAb specifically targeting the IL-13 cytokine, has demonstrated clinical efficacy and safety in patients with moderate-to-severe atopic dermatitis. Tralokinumab binds IL-13 with high affinity, which prevents the interaction of IL-13 with IL-13R\u03b11 and subsequent signaling. Similarly, tralokinumab-bound IL-13 cannot bind to IL-13R\u03b12, a proposed decoy receptor that is reported to bind IL-13 with extraordinarily high affinity. It has however not been fully elucidated to what extent tralokinumab interferes with the endogenous regulation of IL-13 through IL-13R\u03b12. In this mechanistic study, we used biophysical, biochemical, and cellular assays to investigate the effect of tralokinumab on the interaction between IL-13 and IL-13R\u03b11 and IL-13R\u03b12, respectively, as well as the effects on IL-13R\u03b12-mediated IL-13 internalization. We demonstrate that IL-13R\u03b12 binds IL-13 with exceptionally high affinity and that tralokinumab is unable to displace IL-13 from IL-13R\u03b12. In contrast to this, tralokinumab is able to disrupt the IL-13\/IL-13R\u03b11 and IL-13R\u03b11\/IL-13\/IL-4R\u03b1 complex. Furthermore, we demonstrate that whereas the IL-13\/tralokinumab complex is unable to bind IL-13R\u03b12, any IL-13 that is not bound by tralokinumab (i.e., free IL-13) can be bound by IL-13R\u03b12 and subsequently internalized, regardless of the presence of tralokinumab. In summary, our study indicates that tralokinumab does not interfere with endogenous IL-13R\u03b12-mediated regulation of free IL-13.<\/p>\n\n\n\n

Ref: JID Innov 2023<\/a><\/p>\n\n\n\n

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