7F9W

CD25 in complex with Fab

Summary for 7F9W

• Entry DOI: 10.2210/pdb7f9w/pdb
• EMDB information: 31499
• Descriptor: Interleukin-2 receptor subunit alpha, Light chain of Fab, Heavy chain of Fab (3 entities in total)
• Functional Keywords: cd25, antibody, il-2, antitumor protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 92184.34

Authors

Liu, C. (deposition date: 2021-07-05, release date: 2022-01-12, Last modification date: 2024-11-13)

Primary citation

Song, D.,Liu, X.,Dong, C.,Wang, Q.,Sha, C.,Liu, C.,Ning, Z.,Han, J.,Liu, H.,Zong, M.,Zhao, Y.,Li, Y.,Liu, G.,Shao, X.,Dou, C.
Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity.
Sci Rep, 11:22966-22966, 2021

PubMed Abstract: High tumor regulatory T (Treg) cell infiltration is associated with poor prognosis of many cancers. CD25 is highly expressed on tumor Treg cells and is a potential target for Treg deletion. Previously characterized anti-CD25 antibodies appear to have limited efficacy in tumor inhibition. Here we identified two human anti-CD25 antibodies, BA9 and BT942, which did not prevent the activation of IL-2R signaling pathway by IL-2. BT942 had weaker binding and cytotoxic activity to human CD25-expressing cell lines than BA9. But both demonstrated significant tumor growth inhibition in early and late-stage animal cancer models. BT942 resulted in a higher expansion of CD8 T cells and CD4 T cells in tumor microenvironment in mouse MC38 model compared to BA9. BT942 also demonstrated significant higher tumor growth inhibition and higher expansion of CD8 T cells and CD4 T cells in combination with an anti-PD1 antibody. Pharmacokinetic study of BT942 in cynomolgus monkeys demonstrated a half-life of 206.97 ± 19.03 h. Structural analysis by cryo-EM revealed that BT942 recognizes an epitope on opposite side of the CD25-IL-2 binding site, consistent with no IL-2 signaling blockade in vitro. BT942 appears to be an excellent candidate for cancer immunotherapy.

PubMed: 34824364
DOI: 10.1038/s41598-021-02449-y

Experimental method

ELECTRON MICROSCOPY (3.2 Å)