Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Denver, Aurora, CO, USA.
Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Denver, Aurora, CO, USA.
Mol Oncol. 2020 May;14(5):991-1000. doi: 10.1002/1878-0261.12653. Epub 2020 Mar 13.
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.
大多数临床诊断的皮肤 T 细胞淋巴瘤（CTCL）高度表达细胞表面标志物 CC 趋化因子受体 4（CCR4）和/或 CD25。最近，我们开发了基于白喉毒素的重组 Onatak®样人 IL2 融合毒素（IL2 融合毒素）和抗人 CCR4 免疫毒素（CCR4 IT）。在这项研究中，我们首先比较了 CCR4 IT 与 IL2 融合毒素针对人 CD25 CCR4 CTCL 的疗效。我们证明 CCR4 IT 比 IL2 融合毒素更有效。我们进一步构建了 IL2-CCR4 双特异性 IT。双特异性 IT 比 IL2 融合毒素或 CCR4 IT 单独使用更有效。双特异性 IT 是一种有前途的新型靶向治疗药物候选物，可用于治疗难治性和复发性人 CD25 和/或 CCR4 CTCL。
