Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity

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. He...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b0d623a5c8d94c7181dd87241b2b1475
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spelling	oai:doaj.org-article:b0d623a5c8d94c7181dd87241b2b14752021-11-28T12:21:02ZTwo novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity10.1038/s41598-021-02449-y2045-2322https://doaj.org/article/b0d623a5c8d94c7181dd87241b2b14752021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02449-yhttps://doaj.org/toc/2045-2322Abstract 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.Deyong SongXiu LiuChuangchuang DongQiaoping WangChunjie ShaChuan LiuZhenfei NingJing HanHong LiuMengqi ZongYanyan ZhaoYing LiGuangsheng LiuXin ShaoChanglin DouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
description	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.
format	article
author	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
author_facet	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
author_sort	Deyong Song
title	Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
title_short	Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
title_full	Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
title_fullStr	Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
title_full_unstemmed	Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
title_sort	two novel human anti-cd25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b0d623a5c8d94c7181dd87241b2b1475
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Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity

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