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Open data
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Basic information
Entry | Database: PDB / ID: 7f9w | ||||||
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Title | CD25 in complex with Fab | ||||||
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![]() | ANTITUMOR PROTEIN / CD25 / antibody / IL-2 | ||||||
Function / homology | ![]() regulation of T cell tolerance induction / interleukin-2 receptor complex / interleukin-2 receptor activity / interleukin-2 binding / regulation of CD4-positive, alpha-beta T cell proliferation / regulation of T cell homeostatic proliferation / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / interleukin-2-mediated signaling pathway / activated T cell proliferation / inflammatory response to antigenic stimulus ...regulation of T cell tolerance induction / interleukin-2 receptor complex / interleukin-2 receptor activity / interleukin-2 binding / regulation of CD4-positive, alpha-beta T cell proliferation / regulation of T cell homeostatic proliferation / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / interleukin-2-mediated signaling pathway / activated T cell proliferation / inflammatory response to antigenic stimulus / Interleukin-2 signaling / positive regulation of T cell differentiation / activation-induced cell death of T cells / positive regulation of activated T cell proliferation / Interleukin receptor SHC signaling / negative regulation of T cell proliferation / Notch signaling pathway / negative regulation of inflammatory response / RAF/MAP kinase cascade / cell surface receptor signaling pathway / inflammatory response / immune response / external side of plasma membrane / apoptotic process / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Liu, C. | ||||||
![]() | ![]() Title: Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity. Authors: Deyong Song / Xiu Liu / Chuangchuang Dong / Qiaoping Wang / Chunjie Sha / Chuan Liu / Zhenfei Ning / Jing Han / Hong Liu / Mengqi Zong / Yanyan Zhao / Ying Li / Guangsheng Liu / Xin Shao / Changlin Dou / ![]() 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. ...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. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 107.1 KB | Display | ![]() |
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PDB format | ![]() | 83.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 726.6 KB | Display | ![]() |
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Full document | ![]() | 731.1 KB | Display | |
Data in XML | ![]() | 23.1 KB | Display | |
Data in CIF | ![]() | 32.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 31499MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 18354.754 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Antibody | Mass: 24308.867 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Antibody | Mass: 49520.723 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||
Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING ONLY |
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 149373 / Symmetry type: POINT |