Open AccessDosing optimization of CCR 4 immunotoxin for improved depletion of CCR 4 + Treg in nonhuman primates
Author(s) -
Wang Zhaohui,
Louras Nathan J.,
Lellouch Alexandre G.,
Pratts Shan G.,
Zhang Huiping,
Wang Haoyu,
Huang Christene A.,
Cetrulo Curtis L.,
Madsen Joren C.,
Sachs David H.,
Wang Zhirui
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12331
Subject(s) - immunotoxin , ccr4 , diphtheria toxin , dosing , recombinant dna , medicine , immunology , cd22 , pharmacology , immunogenicity , antibody , chemistry , monoclonal antibody , toxin , immune system , chemokine , biochemistry , chemokine receptor , gene
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.