Novel Strategies In Tailoring Human Adenoviruses Into Therapeutic Cancer Gene Therapy Vectors

Gene therapy is a novel approach for the treatment of cancer that has so far not been realized. The scope of this review is to try to define the remaining barriers to the successful use of adenovirus vectors for gene and viral therapy of human tumors and to suggest solutions whereby these barriers can be bypassed. It is the conviction of the authors that too many studies have been performed in animal models that are not sufficiently comprehensive to allow conclusions to be drawn for application in humans. For example, in the case of the murine experimental model, in which most studies have been performed, mice are devoid of circulating antibodies to adenovirus type 5 and adenovirus cannot replicate in mouse cells. While the problems are real enough, as witnessed by the quite limited success in human trials, some of the solutions that will be suggested here are hypothetical and have not as yet been tried, even in animals. The review has no ambition to be exhaustive but is intended as a contribution in order to forward the field of gene therapy vectors for systemic clinical application.