Research Papers:
A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment
PDF | Full Text | Supplementary Files | How to cite | Press Release
Metrics: PDF 264 views | Full Text 513 views | ?
Abstract
Maja Buszko1, Madalyn Jones1, Sruthi Chempati1, Lyra Morina1, Kirstin Ward1, Habtom Habte2, Michael Dziegielewski2 and Ethan M. Shevach1
1 Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
2 Boehringer Ingelheim, Ridgefield, CT 06877, USA
Correspondence to:
Ethan M. Shevach, | email: | [email protected] |
Keywords: Treg; CD25; TME; mAb; GVHD
Received: March 04, 2025 Accepted: June 16, 2025 Published: July 09, 2025
ABSTRACT
Treg play a deleterious role in the tumor microenvironment by suppressing anti-tumor effector T cells. Deletion of Treg can result in an enhanced anti-tumor response. It has been difficult to identify a cell surface antigen that is uniquely expressed on Treg which can be targeted by a deleting mAb. We immunized mice with human Treg cells which had been activated and expanded in vitro. One hybridoma (2B010) which recognized CD25 was identified. 2B010 demonstrated selective reactivity to Treg cells that had been expanded in culture for 5 days, but displayed similar reactivity to a conventional anti-CD25 mAb on freshly expanded Treg. 2B010 did not block the binding of IL-2 in the STAT5 phosphorylation assay and had no effect on the proliferation of Tconv or on Treg suppressor function. It selectively reacted with Treg activated in vivo during xeno-GVHD and produced a selective deletion of Treg from mice undergoing xeno-GVHD. Administration of 2B010 to tumor bearing humanized mice resulted in a profound depletion of Treg from the TME and activation of CD8+ T cells. No effect on tumor growth was observed. 2B010 represents a candidate for treatment of patients with cancer either alone or together with check point inhibitors.

PII: 28752