Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
In: Scientific Reports, Jg. 11 (2021), Heft 1, S. 1-16
Online
unknown
Zugriff:
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.
Titel: |
Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
|
---|---|
Autor/in / Beteiligte Person: | Zhao, Yanyan ; Liu, Chuan ; Mengqi, Zong ; Liu, Hong ; Zhenfei, Ning ; Shao, Xin ; Li, Ying ; Chunjie, Sha ; Changlin, Dou ; Chuangchuang, Dong ; Wang, Qiaoping ; Deyong, Song ; Xiu, Liu ; Liu, Guangsheng ; Jing, Han |
Link: | |
Zeitschrift: | Scientific Reports, Jg. 11 (2021), Heft 1, S. 1-16 |
Veröffentlichung: | Nature Portfolio, 2021 |
Medientyp: | unknown |
ISSN: | 2045-2322 (print) |
Schlagwort: |
|
Sonstiges: |
|