Dosing optimization of <scp>CCR</scp>4 immunotoxin for improved depletion of <scp>CCR</scp>4⁺ Treg in nonhuman primates

Abstract

Recently, we have developed a diphtheria toxin‐based recombinant anti‐human CCR 4 immunotoxin for targeting CCR 4 + tumors and Tregs. In this study, we further optimized the dosing schedule for improved CCR 4 + Treg depletion. We have demonstrated that up to a 90% depletion was achieved and the depletion extended to approximately 2 weeks in the peripheral blood and more than 48 days in the lymph node at 25 μg·kg −1 , BID for 8 consecutive days in cynomolgus monkeys. Expansion was observed including monocytes and NK cells. Antibody against the CCR 4 immunotoxin was detected after approximately 2 weeks, affecting further depletion efficacy for multiple course treatment.