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Title
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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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Author
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Abstract
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| 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 |
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Language
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English
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Source (journal)
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Vaccines
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Publication
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2019
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ISSN
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2076-393X
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DOI
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10.3390/VACCINES7030085
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Volume/pages
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7
:3
(2019)
, 13 p.
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Article Reference
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85
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ISI
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000487982000017
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Pubmed ID
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31394834
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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