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dc.contributor.authorB. John, Lizaen_US
dc.contributor.authorJ. Howland, Lindaen_US
dc.contributor.authorK. Flynn, Jacquelineen_US
dc.contributor.authorC. West, Alisonen_US
dc.contributor.authorDevaud, Christelen_US
dc.contributor.authorP. Duong, Connieen_US
dc.contributor.authorJ. Stewart, Trinaen_US
dc.contributor.authorA. Westwood, Jennyen_US
dc.contributor.authorSheng Guo, Z.en_US
dc.contributor.authorL. Bartlett, Daviden_US
dc.contributor.authorJ. Smyth, Marken_US
dc.contributor.authorH. Kershaw, Michaelen_US
dc.contributor.authorK. Darcy, Phillipen_US
dc.description.abstractOncolytic virotherapy using vaccinia virus (Vv) has shown some encouraging antitumor responses in mouse models and patients, but the breadth of efficacy in clinical trials has been somewhat limited. Given that antitumor effects have correlated with increased host immune responses, we hypothesized that improved therapeutic outcomes may be achieved by using oncolytic virus (OV) in combination with a potent immune agonist reagent. In this study, we carried out a preclinical evaluation of a genetically engineered strain of oncolytic vaccinia virus (Vvdd) for its capacity to induce antitumor responses when combined with an agonist antibody (Ab) specific for the costimulatory molecule 4-1BB (CD137). In immune-competent syngeneic mouse models of cancer, this combination therapy significantly reduced the growth of established subcutaneous tumors relative to either treatment alone. Importantly, the development of pulmonary metastatic lesions was also reduced. Tumor growth inhibition was associated with increased numbers of CD11bnd CD11cyeloid cells in the tumor draining lymph nodes, greater infiltration of CD8ffector T and natural killer (NK) cells, and a more sustained presence of neutrophils at the tumor site. Depletion of T or NK cells or neutrophils reduced efficacy, confirming their contribution to an effective therapeutic response.We further extended this conclusion through results from IFNg deficient mice. In summary, our findings offered a proof-of-concept for a combinatorial approach to enhance the antitumor efficacy of an OV, suggesting a strategy to improve their use as an immunotherapeutic treatment for cancer.en_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalCancer Researchen_US
dc.subject.fieldofresearchTumour Immunologyen_US
dc.titleOncolytic Virus and Anti–4-1BB Combination Therapy Elicits Strong Antitumor Immunity against Established Canceren_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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