Article ; Online: CD25-T
Nature cancer
2020 Volume 1, Issue 12, Page(s) 1153–1166
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 ... ...
| 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. |
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| MeSH term(s) | Animals ; Antibodies, Monoclonal/pharmacology ; Interleukin-2/pharmacology ; Mice ; Neoplasms ; Signal Transduction ; T-Lymphocytes, Regulatory |
| Chemical Substances | Antibodies, Monoclonal ; Interleukin-2 |
| Language | English |
| Publishing date | 2020-11-09 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 2662-1347 |
| ISSN (online) | 2662-1347 |
| DOI | 10.1038/s43018-020-00133-0 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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