7KPG

Blocking Fab 25 anti-SIRP-alpha antibody in complex with SIRP-alpha Variant 1

7KPG の概要

• エントリーDOI: 10.2210/pdb7kpg/pdb
• 分子名称: Heavy chain of Fab 25 anti-SIRP-alpha antibody, Light chain of Fab 25 anti-SIRP-alpha antibody, Tyrosine-protein phosphatase non-receptor type substrate 1, ... (5 entities in total)
• 機能のキーワード: sirpa antibody complex, signal regulatory protein alpha variant 1, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 58197.51

構造登録者

Sim, J.,Pons, J. (登録日: 2020-11-11, 公開日: 2020-12-16, 最終更新日: 2024-10-09)

主引用文献

Kuo, T.C.,Chen, A.,Harrabi, O.,Sockolosky, J.T.,Zhang, A.,Sangalang, E.,Doyle, L.V.,Kauder, S.E.,Fontaine, D.,Bollini, S.,Han, B.,Fu, Y.X.,Sim, J.,Pons, J.,Wan, H.I.
Targeting the myeloid checkpoint receptor SIRP alpha potentiates innate and adaptive immune responses to promote anti-tumor activity.
J Hematol Oncol, 13:160-160, 2020

PubMed Abstract: Signal regulatory protein α (SIRPα) is a myeloid-lineage inhibitory receptor that restricts innate immunity through engagement of its cell surface ligand CD47. Blockade of the CD47-SIRPα interaction synergizes with tumor-specific antibodies and T-cell checkpoint inhibitors by promoting myeloid-mediated antitumor functions leading to the induction of adaptive immunity. Inhibition of the CD47-SIRPα interaction has focused predominantly on targeting CD47, which is expressed ubiquitously and contributes to the accelerated blood clearance of anti-CD47 therapeutics. Targeting SIRPα, which is myeloid-restricted, may provide a differential pharmacokinetic, safety, and efficacy profile; however, SIRPα polymorphisms and lack of pan-allelic and species cross-reactive agents have limited the clinical translation of antibodies against SIRPα. Here, we report the development of humanized AB21 (hAB21), a pan-allelic anti-SIRPα antibody that binds human, cynomolgus monkey, and mouse SIRPα alleles with high affinity and blocks the interaction with CD47.

PubMed: 33256806
DOI: 10.1186/s13045-020-00989-w

実験手法

X-RAY DIFFRACTION (2.27 Å)