Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Jette, Belgium.
Curr Mol Med. 2013 May;13(4):602-25. doi: 10.2174/1566524011313040011.
Over the years, there has been an exponential increase in the number of gene therapy approaches that are under investigation for the treatment of cancer. This can be attributed to our growing understanding of the molecular mechanisms that contribute to the onset and maintenance of cancer as well as to the development of gene delivery vectors. In this review, we will focus on the use of lentiviral vectors (LVs) in immuno gene therapy of cancer, as these efficacious gene delivery vehicles have come to the fore front because of their many attractive features. LVs have been successfully applied to generate potent dendritic cell based anti-cancer vaccines and to deliver cancer-specific receptors to T-cells. Moreover, LVs are under investigation for the modulation of cancer cells. We will describe various strategies of this 'genuine' cancer gene therapy, amongst which transfer of suicide genes, modulation of pro- and anti-apoptotic molecules, strategies to optimize chemo- and radiotherapy, expression of molecules that affect angiogenesis or affect the immunogenicity of tumor cells. These will be discussed in view of our current knowledge of tumor immunology. Finally we will discuss some important issues and future directions to push the field forward.
多年来，针对癌症治疗的基因治疗方法的数量呈指数级增长。这可以归因于我们对导致癌症发生和维持的分子机制的理解不断加深，以及基因传递载体的发展。在这篇综述中，我们将重点介绍慢病毒载体 (LVs) 在癌症免疫基因治疗中的应用，因为这些高效的基因传递载体因其许多吸引人的特性而成为前沿。LV 已成功应用于产生有效的基于树突状细胞的抗癌疫苗，并将癌症特异性受体递送至 T 细胞。此外，LV 正在被研究用于调节癌细胞。我们将描述这种“真正的”癌症基因治疗的各种策略，其中包括自杀基因的转移、促凋亡和抗凋亡分子的调节、优化化疗和放疗的策略、表达影响血管生成或影响肿瘤细胞免疫原性的分子。这些将根据我们对肿瘤免疫学的现有知识进行讨论。最后，我们将讨论一些重要问题和未来方向，以推动该领域的发展。
