May Tobias, Gleiter Stefan, Lilie Hauke
Institut für Biotechnologie, Universität Halle, Kurt Mothes Strasse 3, D-06120, Halle, Germany.
J Virol Methods. 2002 Aug;105(1):147-57. doi: 10.1016/s0166-0934(02)00099-x.
Application of delivery systems in cancer therapy is restricted as a result of the lack of cell specificity of the respective vectors. Recently, a vector system based on virus-like particles (VLPs) of modified polyoma-VP1 was described which were able to bind specifically a tumor-specific antibody fragment, thus directing the vector system towards tumor cells. The functional gene transfer using the VP1 variant VP1-E8C, coupled with the antibody fragment of the tumor-specific antibody B3 is described in this paper. The specific targeting of the antigen expressing cells was highly efficient as determined by fluorescence microscopy. However, only a low percentage of these cells showed a functional gene transfer. This discrepancy could be accounted for by a rather low capacity of the virus like particles to transport DNA and the mechanism of their internalization by the target cells, which led to a lysosomal degradation of the particles. These limitations could be surmounted partially in cell culture experiments, and the principles suitable for applying this vector system in vivo are discussed.
由于各载体缺乏细胞特异性，递送系统在癌症治疗中的应用受到限制。最近，有人描述了一种基于修饰多瘤病毒VP1的病毒样颗粒（VLP）的载体系统，该颗粒能够特异性结合肿瘤特异性抗体片段，从而将载体系统导向肿瘤细胞。本文描述了使用VP1变体VP1-E8C与肿瘤特异性抗体B3的抗体片段进行的功能性基因转移。通过荧光显微镜测定，抗原表达细胞的特异性靶向效率很高。然而，这些细胞中只有一小部分显示出功能性基因转移。这种差异可能是由于病毒样颗粒运输DNA的能力相当低以及它们被靶细胞内化的机制导致颗粒在溶酶体中降解。这些限制在细胞培养实验中可以部分克服，并且讨论了适用于在体内应用该载体系统的原理。
