Bispecific human IL2‐CCR4 immunotoxin targets human cutaneous T‐cell lymphoma

• Published in: Molecular oncology Vol. 14; no. 5; pp. 991 - 1000
• Main Authors: Wang, Haoyu, Wang, Zhaohui, Zhang, Huiping, Qi, Zeng, Johnson, Ariel C., Mathes, David, Pomfret, Elizabeth A., Rubin, Erin, Huang, Christene A., Wang, Zhirui
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2020; John Wiley and Sons Inc; Wiley
• Subjects: Animals; CCR4; CD25 antigen; Cell surface; Chemokines; Cloning; cutaneous T‐cell lymphoma; Deoxyribonucleic acid; Diphtheria; Diphtheria toxin; Diphtheria Toxin - genetics; Diphtheria Toxin - pharmacology; DNA; FDA approval; Flow Cytometry; Humans; IL2; immunotoxin; Immunotoxins - genetics; Immunotoxins - pharmacology; Inhibitory Concentration 50; Interleukin 2; Interleukin-2 - genetics; Interleukin-2 - pharmacology; Interleukin-2 - therapeutic use; Interleukin-2 Receptor alpha Subunit - metabolism; Laboratories; Leukemia; Lymphoma; Lymphoma, T-Cell, Cutaneous - drug therapy; Lymphoma, T-Cell, Cutaneous - mortality; Medical research; Mice; Ontak; R&D; Receptors, CCR4 - genetics; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - pharmacology; Recombinant Proteins; Research & development; Skin; Skin Neoplasms - drug therapy; Surface markers; T-cell lymphoma; Tumors; Xenograft Model Antitumor Assays; United States > US; immunotoxin; Ontak; CCR4; cutaneous T-cell lymphoma; IL2
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1002/1878-0261.12653

The majority of clinically diagnosed cutaneous T‐cell lymphomas (CTCL) highly express the cell‐surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin‐based recombinant Ontak®‐like human IL2 fusion toxin (IL2 fusion toxin) and anti‐human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25+CCR4+ CTCL. We demonstrated that CCR4 IT was more effective than IL2 fusion toxin. We further constructed an IL2‐CCR4 bispecific IT. The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific IT is a promising novel targeted therapeutic drug candidate for the treatment of refractory and recurrent human CD25+ and/or CCR4+ CTCL. We have developed an IL2‐CC chemokine receptor 4 (CCR4) bispecific immunotoxin (IT). The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific IT is a promising novel targeted therapeutic drug candidate for the treatment of refractory and recurrent human CD25+ and/or CCR4+ cutaneous T‐cell lymphoma.