Replicative adenoviruses for cancer therapy

Rapid advances are being made in the engineering of replication-competent v iruses to treat cancer. Adenovirus is a mildly pathogenic human virus that propagates prolifically in epithelial cells, the origin of most human cance rs, While virologists have revealed many details about its molecular intera ctions with the cell, applied scientists have developed powerful technologi es to genetically modify or regulate every viral protein. In tandem, the li mited success of nonreplicative adenoviral vectors in cancer gene therapy h as brought the old concept of adenovirus oncolysis back into the spotlight. Major efforts have been directed toward achieving selective replication by the deletion of viral functions dispensable in tumor cells or by the regul ation of viral genes with tumor-specific promoters. However, the predicted replication selectivity has not been realized because of incomplete knowled ge of the complex virus-cell interactions and the leakiness of cellular pro moters in the viral genome. Capsid modifications are being developed to ach ieve tumor targeting and enhance infectivity, Cellular and viral functions that confer greater oncolytic potency are also being elucidated, Ultimately , the interplay of the virus with the immune system will likely dictate the success of this approach as a cancer therapy.