PolySia-Specific Retargeting of Oncolytic Viruses Triggers Tumor-Specific Immune Responses and Facilitates Therapy of Disseminated XXXX .

@entity1 @entity8236 @entity9504 @entity7245 @entity5 @entity19 @entity2 @entity784 @entity281 @entity151
UNASSIGNED: @entity7245 ( @entity7245 ) is expressed on several malignant @entity5 of neuroendocrine origin, including @entity151 . In this study, we investigated the therapeutic efficacy of @entity5 -directed T-cell responses, elicited by @entity7245 -retargeted oncolytic @entity9504 , in an orthotopic @entity19 model of disseminated @entity2 . In several cell lines, we demonstrated highly @entity7245 -selective retargeting of @entity281 using a bispecific adapter comprising the ectodomain of the coxsackievirus/adenovirus receptor and a @entity7245 -recognizing single-chain antibody domain. PolySia-dependent @entity281 in vivo facilitated effective uptake of viruses in subcutaneous @entity7245 -expressing @entity1 @entity5 , whereas hepatic viral load and hepatotoxicity were significantly reduced. The impact and nature of antitumoral immune responses triggered by systemic delivery of @entity7245 -retargeted oncolytic adenoviruses were investigated in an orthotopic model of disseminated @entity2 . Interestingly, improved transduction by @entity7245 -retargeted oncolytic adenoviruses led to @entity8236 -positive cell infiltrates in close association with large lytic areas. Consistently, enhanced @entity5 regression and prolonged survival was only observed in immunocompetent @entity19 , but not in @entity784 @entity19 . To investigate whether improved @entity281 by @entity7245 retargeting would elicit a @entity5 -specific T-cell response, we screened the used @entity2 cells for mutated oncogenes by complete exon sequencing. In agreement with our other results, only retargeted oncolysis was able to induce a significant response specific for the @entity5 -associated neoepitope Gsta2-Y9H. In conclusion, we demonstrated that effective retargeting of oncolytic adenovirus against @entity7245 -expressing @entity5 elicits an effective @entity5 -directed T-cell response after systemic virus delivery and facilitates therapy of disseminated @entity2 . Cancer Immunol Res; 3(7); 1-13.   2015 AACR.
