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

T play a deleterious role in the tumor microenvironment by suppressing anti-tumor effector T cells. Deletion of T can result in an enhanced anti-tumor response. It has been difficult to identify a cell surface antigen that is uniquely expressed on T which can be targeted by a deleting mAb. We immunized mice with human T cells which had been activated and expanded . One hybridoma (2B010) which recognized CD25 was identified. 2B010 demonstrated selective reactivity to T cells that had been expanded in culture for 5 days, but displayed similar reactivity to a conventional anti-CD25 mAb on freshly expanded T. 2B010 did not block the binding of IL-2 in the STAT5 phosphorylation assay and had no effect on the proliferation of T or on T suppressor function. It selectively reacted with T activated during xeno-GVHD and produced a selective deletion of T from mice undergoing xeno-GVHD. Administration of 2B010 to tumor bearing humanized mice resulted in a profound depletion of T 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.