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.
May
Tobias
T
Institut für Biotechnologie, Universität Halle, Kurt Mothes Strasse 3, D-06120, Halle, Germany.
Gleiter
Stefan
S
Lilie
Hauke
H
D000912:Antibodies, Neoplasm / Q000235:genetics* / Q000378:metabolism; D000918:Antibody Specificity; D001943:Breast Neoplasms; D002277:Carcinoma; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010940:Plant Proteins; D011120:Polyomavirus / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014771:Virion / Q000235:genetics / Q000378:metabolism
D000912:Antibodies, Neoplasm; D004268:DNA-Binding Proteins; D007128:Immunoglobulin Fragments; D010940:Plant Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors