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Materials and methods: C57BL/6 mice were inoculated with B16-melanoma cells expressing human CD20 and ovalbumin. After engraftment, mice received fractionated treatment with non-targeting sdAb or anti-CD20 sdAbs, labeled with the radionuclide 177Lutetium. Different readouts were evaluated: (1) tumor volume, measured by caliper, (2) gene expression profiling of the tumor microenvironment (TME), evaluated using RT-qPCR, (3) immune cell composition of the TME, evaluated using flow cytometry and (4) systemic immune responses, evaluated by stimulation of CD8+ splenocytes with tumor antigens.
Results: A reduced tumor progression was observed upon treatment of CD20+ melanoma-bearing mice. Despite this tumor control, we were not able to document immune activation. Gene expression and flow cytometry analysis did not reveal changes in CD8+ T cells or the inhibitory immune checkpoint PD-1/PD-L1 in the TME. Moreover, CD8+ splenocytes did not show specificity for the antigen ovalbumin, which serves as a surrogate tumor antigen.
Conclusion: Although beta--TRT with 90Yttrium coupled to a tumor-targeting alkylphosphocholine in a model non-Hodgkin Lymphoma was shown to induce immune responses, we were not able to show similar immune activation with 177Lutetium-coupled anti-CD20 sdAbs in a melanoma model. Further research to confirm and study the reason for these contradicting results is required.
|Status||Published - 7 feb 2020|
|Evenement||BACR Annual Meeting 2020: Cancer metastasis: From bedside to bench - Vrije Universiteit Brussel, Campus Jette, Brussels, Belgium|
Duur: 7 feb 2020 → 7 feb 2020
|Conference||BACR Annual Meeting 2020|
|Periode||7/02/20 → 7/02/20|
VingerafdrukDuik in de onderzoeksthema's van 'Investigating immune activation upon beta targeted radionuclide therapy using anti-CD20 single domain antibody fragments in melanoma'. Samen vormen ze een unieke vingerafdruk.
- 4 Actief
ANI184: Nanobody-targeted radionuclide therapy and immune therapy: a perfect match in the area of combination therapy.
1/01/17 → 31/12/21