The development of conditionally replicative adenoviruses for cancer therapy.

Replicative viral agents represent a novel approach for treating neoplastic disease. Tumor cell killing by the viral agent is achieved by direct consequence of the viral replication. Relative sparing of nontumor is, however, required to provide a therapeutic index of utility for cancer treatment. To this end, an ideal viral agent would, thus, possess several logical attributes, including stability and efficiency for infection and lateral spread in vivo, a preference for replication in tumor versus nontumor cells, and the capability of avoiding early detection-and eradication-by the immune system. To date, none of the agents has exhibited optimal characteristics with regard to the aforementioned attributes. Adenovirus, however, has lent itself to a process of extensive engineering that is dealing with each and every one of the major requirements and that is realizing its clinical potential. An advanced understanding of the cancer phenotype, as well as achievements in functionally exploiting viral plasticity, predicate the design and realization of conditionally replicative adenoviral agents with improved characteristics for cancer therapy.