Gene Therapy with Virus Vectors for specific Disease of the Nervous System: Recombinant Retrovirus Vectors for Treatment of Malignant Brain Tumors

Abstract

Publisher Summary The susceptibility of malignant brain tumors of glial origin (gliomas) to virus vector-mediated gene therapy has been investigated only since the early 1990s. The initially favored and best-explored gene therapy approach included insertion of a gene into tumor cells that renders these and their clonal progeny differentially sensitive to drug treatment. The gene/vector system most widely utilized until now is the herpes simplex virus thymidine kinase (HSV-tk) gene transferred by a replication-incompetent retrovirus (RV) vector that is released in situ by fibroblast-derived retrovirus vector-producing cells (RV-VPC). The early work on RV vectors initiated current developments of highly sophisticated third- and fourth-generation virus vectors for human gene therapy. Although, there is an impressive variety of different gene therapy strategies for experimental treatment of brain tumors, their therapeutic success is still very limited and highly dependent on the qualities and limitations of the vector systems available. RV has been one of the earliest vectors used for gene transfer in the brain and employed as a tool for targeted and selective destruction of tumor cells. These vectors seem to be well tolerated and exceptionally biologically safe, although apparently not able to significantly improve survival of the patients in combined treatment protocols.