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

Abstract

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.