Issues

A new investigational affinity-detuned antibody drug conjugate (ADC) optimized to selectively target and deplete intratumoral regulatory T cells (Tregs), which are critical in suppressing antitumor immunity. By detuning its binding affinity to CD25, PF-08046032 minimizes the depletion of peripheral Tregs, thereby lowering the risk of associated autoimmunity. This novel molecule combines a CD25 antibody with the cytotoxic agent monomethyl auristatin E (MMAE), delivering effective antitumor activity through targeted cytotoxicity against Treg but not the effector CD8⁺ T cells. Our presented preclinical studies demonstrate that PF-08046032 effectively depletes tumor-infiltrating Tregs with high CD25 levels while sparing other immune cells, demonstrating its potential as a novel therapeutic approach in advanced malignancies. The graphic was generated in part using BioRender.com. See graphical abstract and read the full article on page 963.