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 deple...

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Detalles Bibliográficos
Autores principales: Wang, Zhaohui, Louras, Nathan J., Lellouch, Alexandre G., Pratts, Shannon G., Zhang, Huiping, Wang, Haoyu, Huang, Christene A., Cetrulo, Curtis L., Madsen, Joren C., Sachs, David H., Wang, Zhirui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068354/
https://www.ncbi.nlm.nih.gov/pubmed/29873181
http://dx.doi.org/10.1002/1878-0261.12331
Descripción
Sumario: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.

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