CD25-targeted antibody–drug conjugate depletes regulatory T cells and eliminates established syngeneic tumors via antitumor immunity

Abstract

This study shows that a PBD dimer-based, CD25-targeted ADC is able to deplete T_regs and eradicate established tumors via antitumor immunity. This represents a novel approach to efficiently deplete T_regs via a very potent DNA damaging toxin known to induce immunogenic cell death. Moreover, this study provides proof of concept for a completely new application of ADCs as immunotherapeutic agents, as the main mode of action relies on the ADC directly targeting immune cells, rather than tumor cells. These strong preclinical data warrant the clinical evaluation of camidanlumab tesirine (ADCT-301), a PBD-based ADC targeting human CD25, either alone or in combination with checkpoint inhibitors in solid tumors with known T_regs infiltration. A phase I trial (NCT03621982) of camidanlumab tesirine in patients with selected advanced solid tumors is ongoing.