Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA;
Cancer Manag Res. 2010 Feb 5;2:53-9. doi: 10.2147/cmar.s5009.
Denileukin diftitox (Ontak(®)) is indicated for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL), a rare lymphoproliferative disorder of the skin. Denileukin diftitox was the first fusion protein toxin approved for the treatment of a human disease. This fusion protein toxin combines the IL2 protein with diphtheria toxin, and targets the CD25 subunit of the IL2 receptor, resulting in the unique delivery of a cytocidal agent to CD-25 bearing T-cells. Historically, immunotherapy targeting malignant T-cells including monoclonal antibodies has been largely ineffective as cytocidal agents compared to immunotherapy directed against B-cells such as rituximab. This review will summarize the development of denileukin diftitox, its proposed mechanism of action, the pivotal clinical trials that led to its FDA approval, the improvements in quality of life, and the common toxicities experienced during the treatment of patients with CTCL. CTCL is often a chronic progressive lymphoma requiring the sequential use of treatments such as retinoids, traditional chemotherapy, or biological response modifiers. The incorporation of the immunotoxin denileukin diftitox into the sequential or combinatorial treatment of CTCL will also be addressed.
地尼白介素二呋替(Onctara(®))适用于治疗持续性或复发性皮肤 T 细胞淋巴瘤(CTCL),这是一种罕见的皮肤淋巴增生性疾病。地尼白介素二呋替是第一个被批准用于治疗人类疾病的融合蛋白毒素。这种融合蛋白毒素将白细胞介素 2(IL2)蛋白与白喉毒素结合,靶向白细胞介素 2 受体的 CD25 亚基,从而将细胞毒性剂独特地递送至携带 CD-25 的 T 细胞。从历史上看,与针对 B 细胞的免疫疗法(如利妥昔单抗)相比,针对恶性 T 细胞的免疫疗法(包括单克隆抗体)作为细胞毒性剂在很大程度上效果不佳。这篇综述将总结地尼白介素二呋替的发展历程、其作用机制、导致其获得 FDA 批准的关键性临床试验、生活质量的改善以及 CTCL 患者治疗过程中常见的毒性。CTCL 通常是一种慢性进行性淋巴瘤,需要序贯使用类视黄醇、传统化疗或生物反应调节剂等治疗方法。地尼白介素二呋替免疫毒素也将被纳入 CTCL 的序贯或联合治疗中。