Development of an E1B, 55 kDa Gene–Deleted, Selectively Replicating
David H. Kirn
The vast majority of human cancers are incurable once metastatic. Chemotherapy and radiotherapy can induce tumor growth inhibition or regression in some cases, but solid tumor progression and resistance to these standard therapeutic modalities inevitably develops. Therefore, new agents with larger therapeutic indices between cancer cells and normal cells are needed. Viruses have been used as gene delivery vectors to cause cancer cell inhibition or killing. One of the major difficulties with this approach, however, is the daunting goal of delivering genes to every cancer cell in the body. In contrast, a replicating viral therapeutic can potentially overcome this limitation. Virus replication in a small fraction of the tumor cells can lead to amplification and spread of the antitumoral effect. Cell killing can be due to viral replication and cell lysis exclusively, or this could be augmented by including additional immunostimulatory or toxin-producing genes.