A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment

TL;DR

A new antibody targets and depletes activated regulatory T cells in the tumor environment, potentially improving cancer treatments.

Contribution

A novel anti-CD25 mAb that preferentially depletes activated Treg cells without affecting their suppressor function is developed.

Findings

2B010 selectively reacts with activated Treg cells in vitro and in vivo.

Administration of 2B010 depletes Treg from the tumor microenvironment and activates CD8+ T cells in humanized mice.

2B010 does not block IL-2 signaling or affect Treg suppressor function.

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.

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