Oncolytic viruses as therapeutic agents

The concept of using viruses as oncolytic agents has a long history, Howeve r, relatively new developments are the use of these viruses as gene deliver y vehicles and the restriction of viral replication and lysis to tumour cel ls. The latter is attempted by the use of tumour-specific promoters, which transcriptionally target viral genes involved in replication, or by deletio n of Viral functions dispensable for replication in tumour cells but essent ial for productive infection of normal cells. In addition, retargeting of t he viral tropism towards tumours by capsid modifications has been examined. Although much progress has been made in developing oncolytic vectors for c linical use, there is still a long way to go to determine which combination s of virus, gene therapy, surgery, radiation, and/or chemotherapy will prov ide improved therapy for the control and eradication of a variety of human cancers, First controlled clinical trials with an oncolytic adenovirus in c ombination with chemotherapy have shown encouraging antineoplastic activity . For future vector developments it will be crucial to achieve maximum vect or distribution and transgene expression within tumours, to trigger a speci fic systemic immune effector response against treated and untreated lesions , and to modulate the immune system to avoid immune-mediated inactivation o r destruction of the virus. In the context of replication-competent vectors , suicide genes might be used as fail-safe mechanism in the case of a runaw ay infection.