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Open AccessArticle

Single Domain Antibody-Mediated Blockade of Programmed Death-Ligand 1 on Dendritic Cells Enhances CD8 T-cell Activation and Cytokine Production

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Laboratory of Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium
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Unit of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium
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Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, 1090 Brussels, Belgium
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Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, 2650 Antwerp, Belgium
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Center for Cell Therapy and Regenerative Medicine, University Hospital Antwerp, 2650 Antwerp, Belgium
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In Vivo Cellular and Molecular Imaging Laboratory, VUB, 1090 Brussels, Belgium
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Nuclear Medicine Department, UZ Brussel, 1090 Brussels, Belgium
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(3), 85; https://doi.org/10.3390/vaccines7030085
Received: 18 June 2019 / Revised: 1 August 2019 / Accepted: 3 August 2019 / Published: 7 August 2019
(This article belongs to the Section Immune Mechanisms)
Dendritic cell [DC] vaccines can induce durable clinical responses, at least in a fraction of previously treated, late stage cancer patients. Several preclinical studies suggest that shielding programmed death-ligand 1 [PD-L1] on the DC surface may be an attractive strategy to extend such clinical benefits to a larger patient population. In this study, we evaluated the use of single domain antibody [sdAb] K2, a high affinity, antagonistic, PD-L1 specific sdAb, for its ability to enhance DC mediated T-cell activation and benchmarked it against the use of the monoclonal antibodies [mAbs], MIH1, 29E.2A3 and avelumab. Similar to mAbs, sdAb K2 enhanced antigen-specific T-cell receptor signaling in PD-1 positive (PD-1pos) reporter cells activated by DCs. We further showed that the activation and function of antigen-specific CD8 positive (CD8pos) T cells, activated by DCs, was enhanced by inclusion of sdAb K2, but not mAbs. The failure of mAbs to enhance T-cell activation might be explained by their low efficacy to bind PD-L1 on DCs when compared to binding of PD-L1 on non-immune cells, whereas sdAb K2 shows high binding to PD-L1 on immune as well as non-immune cells. These data provide a rationale for the inclusion of sdAb K2 in DC-based immunotherapy strategies. View Full-Text
Keywords: human; PD-L1; dendritic cell; vaccination; single domain antibody; nanobody; cancer; immunotherapy human; PD-L1; dendritic cell; vaccination; single domain antibody; nanobody; cancer; immunotherapy
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Broos, K.; Lecocq, Q.; Keersmaecker, B.D.; Raes, G.; Corthals, J.; Lion, E.; Thielemans, K.; Devoogdt, N.; Keyaerts, M.; Breckpot, K. Single Domain Antibody-Mediated Blockade of Programmed Death-Ligand 1 on Dendritic Cells Enhances CD8 T-cell Activation and Cytokine Production. Vaccines 2019, 7, 85.

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