Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy

Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z. Sheng Guo () and David L. Bartlett ()
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Zuqiang Liu: The University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine
Roshni Ravindranathan: The University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine
Pawel Kalinski: The University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine
Z. Sheng Guo: The University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine
David L. Bartlett: The University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour. The dual therapy reduces PD-L1+ cells and facilitates non-redundant tumour infiltration of effector CD8+, CD4+ T cells, with increased IFN-γ, ICOS, granzyme B and perforin expression. Furthermore, the treatment reduces the virus-induced PD-L1+ DC, MDSC, TAM and Treg, as well as co-inhibitory molecules-double-positive, severely exhausted PD-1+CD8+ T cells, leading to reduced tumour burden and improved survival. This combinatorial therapy may be applicable to a much wider population of cancer patients.

Date: 2017
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DOI: 10.1038/ncomms14754

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