Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4+ Treg in nonhuman primates
oleh: Zhaohui Wang, Nathan J. Louras, Alexandre G. Lellouch, Shannon G. Pratts, Huiping Zhang, Haoyu Wang, Christene A. Huang, Curtis L. Cetrulo Jr, Joren C. Madsen, David H. Sachs, Zhirui Wang
| Format: | Article |
|---|---|
| Diterbitkan: | Wiley 2018-08-01 |
Deskripsi
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.