CD25-Treg-depleting antibodies preserving IL-2 signaling on effector T cells enhance effector activation and antitumor immunity

Isabelle Solomon, Maria Amann*, Anne Goubier, Frederick Arce Vargas, Dimitrios Zervas, Chen Qing, Jake Y. Henry, Ehsan Ghorani, Ayse U. Akarca, Teresa Marafioti, Anna Śledzińska, Mariana Werner Sunderland, Dafne Franz Demane, Joanne Ruth Clancy, Andrew Georgiou, Josephine Salimu, Pascal Merchiers, Mark Adrian Brown, Reto Flury, Jan EckmannClaudio Murgia, Johannes Sam, Bjoern Jacobsen, Estelle Marrer-Berger, Christophe Boetsch, Sara Belli, Lea Leibrock, Joerg Benz, Hans Koll, Roger Sutmuller, Karl S. Peggs*, Sergio A. Quezada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Intratumoral regulatory T (Treg) cell abundance associates with diminished antitumor immunity and poor prognosis in human cancers. Recent work demonstrates that CD25, the high-affinity receptor subunit for interleukin (IL)-2, is a selective target for Treg depletion in mouse and human malignancies; however, anti-human CD25 antibodies have failed to deliver clinical responses against solid tumors due to bystander IL-2 receptor signaling blockade on effector T cells, which limits their antitumor activity. Here we demonstrate potent single-agent activity of anti-CD25 antibodies optimized to deplete Treg cells, while preserving IL-2-STAT5 signaling on effector T cells and show synergy with immune checkpoint blockade in vivo. Pre-clinical evaluation of an anti-human CD25 (RG6292) antibody with equivalent features demonstrates, in both nonhuman primates and humanized mouse models, efficient Treg cell depletion with no overt immune-related toxicities. Our data support the clinical development of RG6292 and evaluation of new combination therapies incorporating non-IL-2-blocking anti-CD25 antibodies in clinical studies.

Original languageEnglish
Pages (from-to)1153-1166
Number of pages14
JournalNature Cancer
Issue number12
StatePublished - Dec 2020
Externally publishedYes


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