Journal article

Oncolytic Virus and Anti-4-1BB Combination Therapy Elicits Strong Antitumor Immunity against Established Cancer

Liza B John, Linda J Howland, Jacqueline K Flynn, Alison C West, Christel Devaud, Connie P Duong, Trina J Stewart, Jenny A Westwood, Z Sheng Guo, David L Bartlett, Mark J Smyth, Michael H Kershaw, Phillip K Darcy



Oncolytic 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..

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Funding Acknowledgements

This work was funded by Project Grants from the National Health and Medical Research Council (NHMRC), Cancer Council of Victoria, and the Susan Komen Breast Cancer Foundation. T.J. Stewart was supported by a National Breast Cancer Foundation Fellowship and M.J. Smyth by an NHMRC Australian Research Fellowship. M.H. Kershaw and P.K. Darcy were supported by a NHMRC Senior Research Fellowship and Career Development Award, respectively.