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癌症基因治疗载体

Vectors for cancer gene therapy.

作者信息

Zhang J, Russell S J

机构信息

Cambridge Centre for Protein Engineering, MRC Centre, UK.

出版信息

Cancer Metastasis Rev. 1996 Sep;15(3):385-401. doi: 10.1007/BF00046349.

Abstract

Many viral and non-viral vector systems have now been developed for gene therapy applications. In this article, the pros and cons of these vector systems are discussed in relation to the different cancer gene therapy strategies. The protocols used in cancer gene therapy can be broadly divided into six categories including gene transfer to explanted cells for use as cell-based cancer vaccines; gene transfer to a small number of tumour cells in situ to achieve a vaccine effect; gene transfer to vascular endothelial cells (VECs) lining the blood vessels of the tumour to interfere with tumour angiogenesis; gene transfer to T lymphocytes to enhance their antitumour effector capability; gene transfer to haemopoietic stem cells (HSCs) to enhance their resistance to cytotoxic drugs and gene transfer to a large number of tumour cells in situ to achieve nonimmune tumour reduction with or without bystander effect. Each of the six strategies makes unique demands on the vector system and these are discussed with reference to currently available vectors. Aspects of vector biology that are in need of further development are discussed in some detail. The final section points to the potential use of replicating viruses as delivery vehicles for efficient in vivo gene transfer to disseminated cancers.

摘要

目前已开发出许多病毒和非病毒载体系统用于基因治疗。本文将结合不同的癌症基因治疗策略,讨论这些载体系统的优缺点。癌症基因治疗中使用的方案大致可分为六类,包括将基因转移到体外培养的细胞中用作基于细胞的癌症疫苗;将基因原位转移到少数肿瘤细胞中以达到疫苗效果;将基因转移到肿瘤血管内衬的血管内皮细胞(VECs)中以干扰肿瘤血管生成;将基因转移到T淋巴细胞中以增强其抗肿瘤效应能力;将基因转移到造血干细胞(HSCs)中以增强其对细胞毒性药物的抗性;以及将基因原位转移到大量肿瘤细胞中以实现有或无旁观者效应的非免疫性肿瘤缩小。这六种策略中的每一种都对载体系统提出了独特的要求,并将结合目前可用的载体进行讨论。还将详细讨论载体生物学中需要进一步发展的方面。最后一部分指出了复制病毒作为递送载体在体内将基因有效转移到播散性癌症中的潜在用途。

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