文章：

抗CD19靶向雷帕霉素脂质体诱导伯基特淋巴瘤细胞自噬细胞死亡的新策略

A novel strategy inducing autophagic cell death in Burkitt's lymphoma cells with anti-CD19-targeted liposomal rapamycin

原文发布日期：2014-02-07

DOI: 10.1038/bcj.2014.2

类型: Original Article

开放获取: 是

英文摘要：

Relapsed or refractory Burkitt's lymphoma often has a poor prognosis in spite of intensive chemotherapy that induces apoptotic and/or necrotic death of lymphoma cells. Rapamycin (Rap) brings about autophagy, and could be another treatment. Further, anti-CD19-targeted liposomal delivery may enable Rap to kill lymphoma cells specifically. Rap was encapsulated by anionic liposome and conjugated with anti-CD19 antibody (CD19-GL-Rap) or anti-CD2 antibody (CD2-GL-Rap) as a control. A fluorescent probe Cy5.5 was also liposomized in the same way (CD19 or CD2-GL-Cy5.5) to examine the efficacy of anti-CD19-targeted liposomal delivery into CD19-positive Burkitt’s lymphoma cell line, SKW6.4. CD19-GL-Cy5.5 was more effectively uptaken into SKW6.4 cells than CD2-GL-Cy5.5 in vitro. When the cells were inoculated subcutaneously into nonobese diabetic/severe combined immunodeficiency mice, intravenously administered CD19-GL-Cy5.5 made the subcutaneous tumor fluorescent, while CD2-GL-Cy5.5 did not. Further, CD19-GL-Rap had a greater cytocidal effect on not only SKW6.4 cells but also Burkitt’s lymphoma cells derived from patients than CD2-GL-Rap in vitro. The specific toxicity of CD19-GL-Rap was cancelled by neutralizing anti-CD19 antibody. The survival period of mice treated with intravenous CD19-GL-Rap was significantly longer than that of mice treated with CD2-GL-Rap after intraperitoneal inoculation of SKW6.4 cells. Anti-CD19-targeted liposomal Rap could be a promising lymphoma cell-specific treatment inducing autophagic cell death.

摘要翻译： 

复发或难治性伯基特淋巴瘤尽管采用诱导淋巴瘤细胞凋亡和/或坏死性死亡的强化化疗，预后通常仍较差。雷帕霉素可诱导自噬，或可成为另一种治疗手段。此外，抗CD19靶向脂质体递送技术可能使雷帕霉素特异性杀伤淋巴瘤细胞。研究将雷帕霉素包裹于阴离子脂质体中，并与抗CD19抗体（CD19-GL-Rap）或作为对照的抗CD2抗体（CD2-GL-Rap）偶联。同时采用相同方法将荧光探针Cy5.5脂质体化（CD19/CD2-GL-Cy5.5），以评估抗CD19靶向脂质体在CD19阳性伯基特淋巴瘤细胞系SKW6.4中的递送效率。体外实验显示，CD19-GL-Cy5.5在SKW6.4细胞中的摄取效率显著高于CD2-GL-Cy5.5。将细胞皮下接种至非肥胖糖尿病/重症联合免疫缺陷小鼠后，静脉注射的CD19-GL-Cy5.5可使皮下肿瘤显影，而CD2-GL-Cy5.5则不能。进一步研究发现，CD19-GL-Rap不仅对SKW6.4细胞，对源自患者的伯基特淋巴瘤细胞也表现出比CD2-GL-Rap更强的体外杀细胞效应。这种特异性毒性可被中和性抗CD19抗体所阻断。在腹腔接种SKW6.4细胞的小鼠中，静脉注射CD19-GL-Rap组小鼠的生存期显著长于CD2-GL-Rap组。靶向CD19的脂质体雷帕霉素有望成为通过诱导自噬性死亡实现淋巴瘤细胞特异性治疗的新策略。

原文链接：

A novel strategy inducing autophagic cell death in Burkitt's lymphoma cells with anti-CD19-targeted liposomal rapamycin