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.

中文翻译：

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双特异性人IL2-CCR4免疫毒素靶向人皮肤T细胞淋巴瘤。

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Ontak®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融合毒素靶向人CD25 + CCR4 + CTCL的功效。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比单独的IL2融合毒素或CCR4 IT更有效。双特异性IT是用于治疗难治性和复发性人CD25 +和/或CCR4 + CTCL的有希望的新型靶向治疗药物候选物。