Projecten per jaar
Samenvatting
Targeted radionuclide therapy (TRT) using probes labeled with Lutetium-177 represents a new and growing type of cancer therapy. We studied immunological changes in response to TRT with Lutetium-177 labeled anti-human CD20 camelid single domain antibodies (sdAbs) in a B16-melanoma model transfected to express human CD20, the target antigen, and ovalbumin, a surrogate tumor antigen. High-dose TRT induced melanoma cell death, calreticulin exposure and ATP-release in vitro. Melanoma-bearing mice received fractionated low and high-dose TRT via tumor targeting anti-human CD20 sdAbs, as opposed to control sdAbs. Tumor growth was delayed with both doses. Low and high-dose TRT increased interleukin-10 serum levels. Low-dose TRT also decreased CCL5 serum levels. At the tumor, high-dose TRT induced a type I interferon gene signature, while low-dose TRT induced a pro-inflammatory gene signature. Low and high-dose TRT increased the percentage of PD-L1pos and PD-L2pos myeloid cells in tumors with a marked increase in alternatively activated macrophages after high-dose TRT. The percentage of tumor-infiltrating T-cells was not changed, yet a modest increase in ovalbumin-specific CD8pos T-cells was observed after low-dose TRT. Contradictory, low and high-dose TRT decreased CD4pos T helper 1 (Th1)-cells in addition to double negative T-cells. In conclusion, these data suggest that low and high-dose TRT induce distinct immunological changes, which might serve as an anchoring point for combination therapy.
Originele taal-2 | English |
---|---|
Pagina's (van-tot) | 1136-1148 |
Aantal pagina's | 13 |
Tijdschrift | Molecular Cancer Therapeutics |
Volume | 21 |
Nummer van het tijdschrift | 7 |
Vroegere onlinedatum | 2022 |
DOI's | |
Status | Published - jul 2022 |
Bibliografische nota
©2022 The Authors; Published by the American Association for Cancer Research.Vingerafdruk
Duik in de onderzoeksthema's van 'Targeted radionuclide therapy with low and high-dose Lutetium-177 labeled single domain antibodies induces distinct immune signatures in a mouse melanoma model'. 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
Onderzoekersoutput
- 11 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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Targeted Radionuclide Therapy with Low and High-Dose Lutetium-177-Labeled Single Domain Antibodies Induces Distinct Immune Signatures in a Mouse Melanoma Model
Breckpot, K. (Creator) & Ertveldt, T. (Creator), Molecular Cancer Therapy, 16 dec 2024
DOI: https://doi.org/10.1158/1535-7163.c.6543403.v1
Dataset
Activiteiten
- 1 Talk or presentation at a workshop/seminar
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SCK NMA-talk
Thomas Ertveldt (Presenter), Nick Devoogdt (Invited speaker) & Matthias D'Huyvetter (Contributor)
14 nov 2023Activiteit: Talk or presentation at a workshop/seminar