The host response to cancer virotherapy.
Clinical trials of oncolytic viruses (OVs) for cancers have revealed that these agents are well tolerated. However, clear-cut evidence of efficacy has been elusive. Although investigators are attempting to generate more efficacious OVs, a fundamental issue continues to limit the efficacy of cancer virotherapy - the response of the host to the ongoing viral infection. This response occurs at the level of intracellular tumor defenses to the viral infection, extracellular stromal reactions to the propagating virus, and, importantly, active host defenses consisting of innate immune as well as inflammatory angiogenic responses. The combination of these host responses severely limits and curtails tumor cell infection and viral replication, thus limiting anticancer efficacy. We believe that such host responses have to be circumvented, at least temporarily or partially, or both, in order to fulfill the promising anticancer effects of these agents.
Chiocca
E Antonio
EA
The Ohio State University Medical Center, Dardinger Neuro-oncology Center, Department of Neurosurgery, James Comprehensive Cancer Center, N-1017 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210-1240, USA. EA.Chiocca@osumc.edu
D000818:Animals; D006801:Humans; D007109:Immunity / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D050130:Oncolytic Virotherapy