Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4 + Treg in nonhuman primates.

Recently, we have developed a diphtheria toxin-based recombinant anti-human CCR4 immunotoxin for targeting CCR4(+) tumors and Tregs. In this study, we further optimized the dosing schedule for improved CCR4(+) Treg depletion. We have demonstrated that up to a 90% depletion was achieved and the depletion extended to approximately 2weeks in the peripheral blood and more than 48days in the lymph node at 25gkg(-1), BID for 8 consecutive days in cynomolgus monkeys. Expansion was observed including monocytes and NK cells. Antibody against the CCR4 immunotoxin was detected after approximately 2weeks, affecting further depletion efficacy for multiple course treatment.