Adenovirus-based cancer gene therapy

Over the past decade, adenovirus (Ad)-based vectors have been used extensively in the context of cancer gene therapy. Two basic strategies have been pursued for the use of Ad vectors in cancer gene therapy: 1) approaches aimed at direct tumor cell killing through delivery of replicating oncolytic viruses or non-replicating vectors encoding tumor suppressor genes, suicide genes or anti-angiogenic genes, and 2) immunotherapeutic approaches aimed at inducing host antitumor immune responses that can destroy tumor cells at both primary and metastatic locations. Both strategies offer the potential of selective tumor cell destruction without damage to normal tissues. Extensive pre-clinical and clinical studies have been conducted based on these strategies. Encouraging results have been obtained but robust clinical efficacy remains elusive. Several obstacles limiting the therapeutic activity of Ad vectors have been encountered, including efficiency of tumor cell transduction and inhibition of efficacy by anti-Ad host immune responses. However, expanding knowledge in the areas of Ad biology and tumor biology continues to lead to increasingly sophisticated approaches to address these issues. A review of various Ad-based cancer gene therapy approaches and recent progress in the area are presented herein.