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

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 ?g·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.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6068354 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Wang Zhaohui Z Louras Nathan J NJ Lellouch Alexandre G AG Pratts Shannon G SG Zhang Huiping H Wang Haoyu H Huang Christene A CA Cetrulo Curtis L CL Madsen Joren C JC Sachs David H DH Wang Zhirui Z

Molecular oncology 20180703 8

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. Ex ...[more]

PMID: 29873181

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