Projecten per jaar
Samenvatting
Methods: We performed non-invasive whole-body imaging to visualize PD-L1 expression at different timepoints after vaccination of melanoma-bearing mice. Mice bearing ovalbumin (OVA) expressing B16 tumors were i.v. injected with the Galsome mRNA vaccine: OVA encoding mRNA lipoplexes co-encapsulating a low or a high dose of the atypical adjuvant α-galactosylceramide (αGC) to activate invariant natural killer T (iNKT) cells. Serial non-invasive whole-body immune imaging was performed using a technetium-99m (99mTc)-labeled anti-PD-L1 nanobody, single-photon emission computerized tomography (SPECT) and X-ray computed tomography (CT) images were quantified. Additionally, cellular expression of PD-L1 was evaluated with flow cytometry.
Results: SPECT/CT-imaging showed a rapid and systemic upregulation of PD-L1 after vaccination. PD-L1 expression could not be correlated to the αGC-dose, although we observed a dose-dependent iNKT cell activation. Dynamics of PD-L1 expression were organ-dependent and most pronounced in lungs and liver, organs to which the vaccine was distributed. PD-L1 expression in lungs increased immediately after vaccination and gradually decreased over time, whereas in liver, vaccination-induced PD-L1 upregulation was short-lived. Flow cytometric analysis of these organs further showed myeloid cells as well as non-immune cells with elevated PD-L1 expression in response to vaccination. SPECT/CT imaging of the tumor demonstrated that the expression of PD-L1 remained stable over time and was overall not affected by vaccination although flow cytometric analysis at the cellular level demonstrated changes in PD-L1 expression in various immune cell populations following vaccination.
Conclusion: Repeated non-invasive whole-body imaging using 99mTc-labeled anti-PD-L1 nanobodies allows to document the dynamic nature of PD-L1 expression upon vaccination. Galsome vaccination rapidly induced systemic upregulation of PD-L1 expression with the most pronounced upregulation in lungs and liver while flow cytometry analysis showed upregulation of PD-L1 in the tumor microenvironment. This study shows that imaging using nanobodies may be useful for monitoring vaccine-mediated PD-L1 modulation in patients and could provide a rationale for combination therapy. To the best of our knowledge, this is the first report that visualizes PD-L1 expression upon cancer vaccination.
Originele taal-2 | English |
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Pagina's (van-tot) | 5483-5500 |
Aantal pagina's | 18 |
Tijdschrift | Theranostics |
Volume | 13 |
Nummer van het tijdschrift | 15 |
DOI's | |
Status | Published - 9 okt 2023 |
Bibliografische nota
Publisher Copyright:© The author(s).
Vingerafdruk
Duik in de onderzoeksthema's van 'Nanobody-mediated SPECT/CT imaging reveals the spatiotemporal expression of programmed death-ligand 1 in response to a CD8+ T cell and iNKT cell activating mRNA vaccine'. Samen vormen ze een unieke vingerafdruk.-
SRP83: SRP-Onderzoekszwaartepunt: Immunoregulatoire cellen als doelwit voor moleculaire beeldvorming en therapie in inflammatoire ziekten en kanker
Van Ginderachter, J., Lahoutte, T., Lahoutte, T., Van Ginderachter, J., Devoogdt, N., Raes, G., Stijlemans, B., Vincke, C. & De Groof, T.
1/11/22 → 31/10/27
Project: Fundamenteel
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SRP62: SRP-Groeifinanciering: Single-domain antibody fragment (SdAb)-based TArgeted Radionuclide Therapy: STaRT programme
Keyaerts, M., D'Huyvetter, M. & Neyns, B.
1/03/19 → 30/09/24
Project: Fundamenteel
Onderzoekersoutput
- 6 Citaties
- 1 PhD Thesis
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Radiolabeled single-domain antibodies as a means to evoke and monitor immunological responses in malignant lesions
Ertveldt, T., 2023, 177 blz.Onderzoeksoutput: PhD Thesis
Open AccessBestand
Datasets
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Nanobody-mediated SPECT/CT imaging reveals the spatiotemporal expression of programmed death-ligand 1 in response to a CD8+ T cell and iNKT cell activating mRNA vaccine
Breckpot, K. (Creator) & Ertveldt, T. (Creator), Theranostics, 16 dec 2024
Dataset
Prijzen
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Marie-Louise Lottin Award
Ertveldt, Thomas (Recipient), nov 2024
Prijs: Prize (including medals and awards)
Bestand