anti-CD25 antibody-drug conjugate PF-08046032

An antibody-drug conjugate (ADC) composed of a detuned-affinity monoclonal antibody directed against CD25 (interleukin-2 receptor subunit alpha; IL-2R alpha; IL-2Ra), conjugated to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, anti-CD25 ADC PF-08046032 targets and binds to CD25 expressed on tumor-infiltrating regulatory T (Treg) cells. Upon internalization and the release of MMAE, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in the Treg cells. This depletes Treg cells in the tumor microenvironment (TME) and prevents immunosuppression, thereby enhancing anti-tumor immune responses. CD25, the alpha chain of the IL-2 receptor, is highly expressed on Treg cells but not on effector T (Teff) cells in tumors.