title: The immunologic aspects of poxvirus oncolytic therapy.
abstract: The concept of using replicating oncolytic viruses in cancer therapy dates to the beginning of the twentieth century. However, in the last few years, an increasing number of pre-clinical and clinical trials have been carried out with promising preliminarily results. Novel, indeed, is the suggestion that viral oncolytic therapy might not operate exclusively through an oncolysis-mediated process but additionally requires the "assistance" of the host's immune system. Originally, the host's immune response was believed to play a predominant obstructive role against viral replication, hence limiting the anti-tumor efficacy of viral vectors. Recent data, however, suggest that the immune response may also play a key role in promoting tumor destruction in association with the oncolytic process. In fact, immune effector pathways activated during oncolytic virus-induced tumor rejection seem to follow a similar pattern to those observed when the broader phenomenon of immune-mediated tissue-specific rejection occurs in other immune-related pathologies. We recently formulated the "Immunologic Constant of Rejection" hypothesis, emphasizing commonalties in transcriptional patterns observed when tissue-destruction occurs: whether with a favorable outcome, such as in tumor rejection and pathogen clearance; or a destructive one, such as in allograft rejection or autoimmunity. Here, we propose that a similar mechanism induces clearance of virally infected tumors and that such a mechanism is primarily dependent on innate immune functions.
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA. worschecha@mail.nih.gov
authors.forename: Andrea
authors.initials: A
authors.lastname: Worschech
authors.forename: D
authors.initials: D
authors.lastname: Haddad
authors.forename: D F
authors.initials: DF
authors.lastname: Stroncek
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D003588:Cytopathogenic Effect, Viral / Q000235:genetics / Q000276:immunology*; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D050130:Oncolytic Virotherapy; D011212:Poxviridae / Q000235:genetics*