Projects per year
Abstract
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.
Original language | English |
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Article number | 85 |
Pages (from-to) | E85-E85 |
Number of pages | 5 |
Journal | Vaccines |
Volume | 7 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Sep 2019 |
Keywords
- human
- PD-L1
- dendritic cell
- vaccination
- single domain antibody
- nanobody
- cancer
- immunotherapy
- Human
- Dendritic cell
- Nanobody
- Vaccination
- Single domain antibody
- Immunotherapy
- Cancer
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SRP48: Strategic Research Programme: Cancer Cell Targeting in Myeloma and Melanoma (MyMe)
Vanderkerken, K., Thielemans, K., Vanderkerken, K. & Breckpot, K.
1/11/17 → 31/10/24
Project: Fundamental
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FWOSB81: Eccentric: Enhancing the function of Cancer Countering Effector cells using Nanobodies Targeting Regulatory Immune Checkpoints
Breckpot, K., Devoogdt, N., Keyaerts, M. & Awad, R. M.
1/11/19 → 31/10/23
Project: Fundamental
Activities
- 1 Talk or presentation at a conference
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Non-invasive immune imaging and cancer immunotherapy using human PD-L1
Karine Breckpot (Speaker)
9 Sep 2021Activity: Talk or presentation › Talk or presentation at a conference