Unknown

Dataset Information

0

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


ABSTRACT: Intratumoral regulatory T cell (Treg) abundance associates with diminished anti-tumor immunity and poor prognosis in human cancers. Recent work demonstrates that CD25, the high affinity receptor subunit for 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 anti-tumor activity. Here we demonstrate potent single-agent activity of anti-CD25 antibodies optimized to deplete Tregs whilst preserving IL-2-STAT5 signaling on effector T cells, and demonstrate synergy with immune checkpoint blockade in vivo. Pre-clinical evaluation of an anti-human CD25 (RG6292) antibody with equivalent features demonstrates, in both non-human primates and humanized mouse models, efficient Treg depletion with no overt immune-related toxicities. Our data supports the clinical development of RG6292 and evaluation of novel combination therapies incorporating non-IL-2 blocking anti-CD25 antibodies in clinical studies.

SUBMITTER: Solomon I 

PROVIDER: S-EPMC7116816 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2493000 | biostudies-other
| S-EPMC5509332 | biostudies-literature
| S-EPMC10907296 | biostudies-literature
| S-EPMC6511047 | biostudies-literature
| S-EPMC8222404 | biostudies-literature
| S-EPMC3613918 | biostudies-literature
| S-EPMC2212985 | biostudies-literature
| S-EPMC6934597 | biostudies-literature
| S-EPMC5215247 | biostudies-literature
| S-EPMC7887758 | biostudies-literature