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. 2023 Aug 17;14:1228486. doi: 10.3389/fimmu.2023.1228486

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Copyright © 2023 Salek-Ardakani, Zajonc and Croft

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Structural superposition of several agonist modalities targeting human 4-1BB. 4-1BB in graded grey surface representation, with individual cysteine-rich domains (CRD’s) labeled. (A) outer view of 4-1BB. (B) inner view of 4-1BB, highlighting the 4-1BBL binding sites in yellow. Only utomilumab and the BCY10916 peptide block binding of 4-1BBL to 4-1BB, while urelumab, ALG.APV-527, and PM1003-VHH, allow for simultaneous binding with 4-1BBL. BCY10916 is a close analog of the cyclic 4-1BB binding peptide found in the EphA2/4-1BB bispecific BCY12491.