Oncolytic virotherapy is emerging as a promising approach for the treatment ofseveral neoplasms. The term "oncolytic viruses" is generally employed to indicatenaturally occurring or genetically engineered attenuated viral particles thatcause the demise of malignant cells while sparing their non-transformedcounterparts. From a conceptual standpoint, oncolytic viruses differ fromso-called "oncotropic viruses" in that only the former are able to kill cancercells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several different steps of the viralcycle, including the entry of virions (transductional specificity) as well astheir intracellular survival and replication (post-transcriptional andtranscriptional specificity). During the past two decades, a large array ofreplication-competent and replication-incompetent oncolytic viruses has beendeveloped and engineered to express gene products that would specifically promotethe death of infected (cancer) cells. However, contrarily to long-standingbeliefs, the antineoplastic activity of oncolytic viruses is not a mereconsequence of the cytopathic effect, i.e., the lethal outcome of an intense,productive viral infection, but rather involves the elicitation of an antitumorimmune response. In line with this notion, oncolytic viruses genetically modifiedto drive the local production of immunostimulatory cytokines exert more robusttherapeutic effects than their non-engineered counterparts. Moreover, theefficacy of oncolytic virotherapy is significantly improved by some extent ofinitial immunosuppression (facilitating viral replication and spread) followed bythe administration of immunostimulatory molecules (boosting antitumor immuneresponses). In this Trial Watch, we will discuss the results of recent clinicaltrials that have evaluated/are evaluating the safety and antineoplastic potentialof oncolytic virotherapy.
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