Assessment of cell type specific gene transfer of polyoma virus like particles presenting a tumor specific antibody Fv fragment

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.