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

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

Publication date: Aug 07, 2019

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-1) reporter cells activated by DCs. We further showed that the activation and function of antigen-specific CD8 positive (CD8) 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.

Broos, K., Lecocq, Q., Keersmaecker, B., Raes, G., Corthals, J., Lion, E., Thielemans, K., Devoogdt, N., Keyaerts, M., and Breckpot, K. Single Domain Antibody-Mediated Blockade of Programmed Death-Ligand 1 on Dendritic Cells Enhances CD8 T-cell Activation and Cytokine Production. 23704. 2019 Vaccines (Basel) (7):3.

Concepts Keywords
Affinity Vaccination
Antigen Immunotherapy
Basel Medical specialties
CD8 Medicine
Cytokine Immune system
Immune Cells Branches of biology
Immunotherapy Immunology
K2 Cytotoxic T cell
Ligand PD-L1
Monoclonal Antibodies Cancer immunotherapy
T Cell Antibodies
T Cell Receptor

Semantics

Type Source Name
drug DRUGBANK Cycloserine
gene UNIPROT RPL17
drug DRUGBANK Avelumab
gene UNIPROT CASP4
gene UNIPROT CD274
disease DOID cancer
disease MESH cancer
disease MESH Death

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