Gene Therapy and Virus-Based Cancer Vaccines

Abstract

Since cancer is a genetic disease, the possibility of correcting defective genes would appear to be a highly promising approach to its treatment. However, the use of gene therapy has been limited by the inability to deliver a therapeutic gene to every cell in the tumor and by the heterogeneity in the enabling mutations found both between and within tumors. However, recent advances in the design of both viral (including non-replicating and oncolytic, or selectively replicating viruses) and non-viral gene delivery vehicles have allowed for more efficient and selective delivery of therapeutic genes to tumor cells leading to greater and longer term gene expression. In addition, a more realistic assessment of how genetic material most likely produce the greatest anti-tumor effect when expressed from within only a portion of cells in the tumor has resulted in the evolution of vectors that have demonstrated anti-tumor effects in the clinical setting and will likely result in approved therapies that can truly benefit the patient population. In particular, the capacity to induce a bystander effect, in a way that killing cells within the tumor which might not have been transfected directly with the genetic material be affected is an important property of most successful cancer gene therapies. As such, genes whose products induce an anti-tumor immune response within and against the tumor have been especially successful, as well as genes that can sensitize tumors to chemotherapies (such as through pro-drug conversion) or that target angiogenesis within the tumor. These can be used alone, or in combination with other therapies and many have now demonstrated potential in the clinical setting. Here, we describe the advantages and limitations of the current leading viral and non-viral gene delivery systems; assess the potential and proven capabilities of different therapeutic genes expressed from within the tumor, with special focus on immune-modulating genes and vaccines; and provide an overview of the use of oncolytic viruses as both therapies and gene expression vehicles.