Non-replicating adenoviral vectors for cancer gene therapy.

While there are many choices among gene transfer vectors for basic or applied research, non-replicating adenoviruses are among the most studied. The virus is well suited for in vivo gene therapy since the vector can be produced with relatively high titers, is an efficient platform for in vivo modification of a variety of target cells and is relatively safe considering that the viral genome remains episomal. The production of adenoviral vectors is scalable and, once virus particles have been recovered, does not depend on the transfection of plasmids, a costly and laborious process to perform on large scale and with pharmaceutical quality. These vectors can be extensively modified to provide targeting at the level of transduction and transgene expression. The use of a non-replicating vector implies that it will not express viral proteins but instead can be modified to carry coding or non-coding sequences, including those that may be prejudicial to the life cycle of replicating viruses. Admittedly, immunogenicity of adenoviral vectors is an issue that requires careful consideration but may be leveraged to act as an adjuvant for vaccines or to overcome the immunosuppressive tumor microenvironment. Modifications also allow adenoviral vectors to act as important allies for achieving long-term expression. If viral replication is desired, non-replicating vectors can be paired with conditionally replicating adenovirus, thus providing the best of both approaches. To date, three cancer gene therapy products, Gendicine, Adstiladrin, and Papzimeos, that are based on non-replicating adenovirus have been approved for commercialization. As we will explore here, non-replicating adenoviral vectors continue to be developed for cancer gene therapy.