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

Wang Z, Louras NJ, Lellouch AG, Pratts SG, Zhang H, Wang H, Huang CA, Cetrulo CL, Madsen JC, Sachs DH, Wang Z Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4+ Treg in Non-Human Primates Mol Oncol. 2018 Jun 5. doi: 10.1002/1878-0261.12331.

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Abstract

Abstract

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 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 CCR4 immunotoxin was detected after approximately 2 weeks, affecting further depletion efficacy for multiple course treatment.