基因工程改造的携带兔羧酸酯酶的人神经干细胞可靶向中枢神经系统淋巴瘤。
Genetically-engineered human neural stem cells with rabbit carboxyl esterase can target CNS lymphoma.
机构信息
Department of Neurosurgery, Samsung Medical Centre and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea. Tel: +82 234103497,
出版信息
Anticancer Res. 2013 Dec;33(12):5335-42.
BACKGROUND
Despite advances in its treatment, CNS lymphoma remains a devastating disease. Taking advantage of the tumour-tropic properties of neural stem cells (NSCs) is a novel therapeutic strategy. To apply this strategy to the treatment of CNS lymphoma, we investigated the role of NSCs expressing carboxyl esterase (HB1.F3.CE), which activates irinotecan.
MATERIALS AND METHODS
In order to find in vitro bystander effects of engineered NSCs, we performed cell viability assays. In vivo, the HB1.F3.CE cells were injected into the brain of mice with orthotopic CNS lymphoma. Mice were then treated with irinotecan by systemic administration.
RESULTS
The HB1.F3.CE cells significantly inhibited the growth of Raji cells with irinotecan treatment. In vivo, the HB1.F3.CE cells migrated into the tumour and significantly reduced tumour volume. In addition, survival of mice was prolonged by treatment with HB1.F3.CE and irinotecan.
CONCLUSION
Transplantation of human NSCs encoding CE into brain, combined with irinotecan therapy, may be an effective treatment regimen for CNS lymphoma.
背景
尽管中枢神经系统淋巴瘤的治疗取得了进展，但它仍然是一种毁灭性的疾病。利用神经干细胞（NSCs）的肿瘤趋向性是一种新的治疗策略。为了将这种策略应用于中枢神经系统淋巴瘤的治疗，我们研究了表达羧酸酯酶（HB1.F3.CE）的 NSCs 的作用，该酶能激活伊立替康。
材料和方法
为了在体外寻找工程化 NSCs 的旁观者效应，我们进行了细胞活力测定。在体内，将 HB1.F3.CE 细胞注射到患有中枢神经系统淋巴瘤的小鼠的脑内。然后通过系统给药用伊立替康对小鼠进行治疗。
结果
HB1.F3.CE 细胞在伊立替康处理下显著抑制了 Raji 细胞的生长。在体内，HB1.F3.CE 细胞迁移到肿瘤中，显著减少了肿瘤体积。此外，用 HB1.F3.CE 和伊立替康治疗延长了小鼠的存活时间。
结论
将编码 CE 的人 NSCs 移植到脑内，并结合伊立替康治疗，可能是中枢神经系统淋巴瘤的有效治疗方案。
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