Enzon Pharmaceuticals, Inc., 20 Kingsbridge Road, Piscataway, NJ 08854, USA.
Haematologica. 2009 Oct;94(10):1456-9. doi: 10.3324/haematol.2009.008276.
Examination of the clinical utility of SN38 (10-hydroxy-7-ethyl-camptothecin), the active metabolite of CPT-11, has not been possible to date due to poor solubility of SN38. Here we evaluated the activity of EZN-2208, a water-soluble polyethyleneglycol-SN38 conjugate, in pre-clinical models of Burkitt's non-Hodgkin's lymphoma (NHL) (Raji and Daudi), and follicular NHL (DoHH2). In vitro, the IC50 of EZN-2208 ranged from 3-24 nM, which was 30- to 45-fold lower than CPT-11 or 2.5- to 3.5-fold higher than SN38. In both an early-disease Raji model and an advanced-disease Daudi model, treatment with multiple doses of EZN-2208 resulted in 90% and 100% cures of animals, respectively (cure defined as no sign of tumors by gross observations at the termination of study). The activity of EZN-2208 was dramatically superior to that of CPT-11 in all three models. The excellent therapeutic efficacy of EZN-2208 in several B-cell NHL xenograft models merits its evaluation in the clinic for lymphoid malignancies.
由于 SN38（喜树碱 11 的活性代谢物）的溶解度较差，迄今为止，尚未对其临床实用性进行检查。在这里，我们评估了水溶性聚乙二醇-SN38 缀合物 EZN-2208 在伯基特氏非霍奇金淋巴瘤（NHL）（Raji 和 Daudi）和滤泡性 NHL（DoHH2）的临床前模型中的活性。在体外，EZN-2208 的 IC50 范围为 3-24 nM，比 CPT-11 低 30-45 倍，比 SN38 高 2.5-3.5 倍。在早期疾病 Raji 模型和晚期疾病 Daudi 模型中，用多剂量 EZN-2208 治疗分别导致 90%和 100%的动物治愈（治愈定义为在研究结束时通过大体观察没有肿瘤迹象）。EZN-2208 的活性在所有三种模型中均明显优于 CPT-11。EZN-2208 在几种 B 细胞 NHL 异种移植模型中的优异治疗效果证明其在临床上用于治疗淋巴恶性肿瘤是合理的。
