Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap

Wantong Song, Limei Shen, Ying Wang, Qi Liu, Tyler J. Goodwin, Jingjing Li, Olekasandra Dorosheva, Tianzhou Liu, Rihe Liu () and Leaf Huang ()
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Wantong Song: University of North Carolina
Limei Shen: University of North Carolina
Ying Wang: University of North Carolina
Qi Liu: University of North Carolina
Tyler J. Goodwin: University of North Carolina
Jingjing Li: University of North Carolina
Olekasandra Dorosheva: University of North Carolina
Tianzhou Liu: The Second Hospital of Jilin University
Rihe Liu: University of North Carolina
Leaf Huang: University of North Carolina

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Although great success has been obtained in the clinic, the current immune checkpoint inhibitors still face two challenging problems: low response rate and immune-related adverse effects (irAEs). Here we report the combination of immunogenic chemotherapy and locally expressed PD-L1 trap fusion protein for efficacious and safe cancer immunotherapy. We demonstrate that oxaliplatin (OxP) boosts anti-PD-L1 mAb therapy against murine colorectal cancer. By design of a PD-L1 trap and loading its coding plasmid DNA into a lipid-protamine-DNA nanoparticle, PD-L1 trap is produced transiently and locally in the tumor microenvironment, and synergizes with OxP for tumor inhibition. Significantly, unlike the combination of OxP and anti-PD-L1 mAb, the combination of OxP and PD-L1 trap does not induce obvious Th17 cells accumulation in the spleen, indicating better tolerance and lower tendency to irAEs. The reports here may highlight the potential of applying PD-L1 inhibitor, especially locally expressed PD-L1 trap, in cancer therapy following OxP-based chemotherapy.

Date: 2018
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DOI: 10.1038/s41467-018-04605-x

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