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

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