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TitleTwo novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity.
Journal, issue, pagesSci Rep, Vol. 11, Issue 1, Page 22966, Year 2021
Publish dateNov 25, 2021
AuthorsDeyong 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 /
PubMed AbstractHigh 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.
External linksSci Rep / PubMed:34824364 / PubMed Central
MethodsEM (single particle)
Resolution3.2 Å
Structure data

31499

7f9w

EMDB-31499, PDB-7f9w:
CD25 in complex with Fab
Method: EM (single particle) / Resolution: 3.2 Å

Source
  • homo sapiens (human)
KeywordsANTITUMOR PROTEIN / CD25 / antibody / IL-2

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