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Anti-Human PD-L1 Nanobody for Immuno-PET Imaging: Validation of a Conjugation Strategy for Clinical Translation
- Source :
- Biomolecules, Vol 10, Iss 10, p 1388 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Immune checkpoints, such as programmed death-ligand 1 (PD-L1), limit T-cell function and tumor cells use this ligand to escape the anti-tumor immune response. Treatments with monoclonal antibodies blocking these checkpoints have shown long-lasting responses, but only in a subset of patients. This study aims to develop a Nanobody (Nb)-based probe in order to assess human PD-L1 (hPD-L1) expression using positron emission tomography imaging, and to compare the influence of two different radiolabeling strategies, since the Nb has a lysine in its complementarity determining region (CDR), which may impact its affinity upon functionalization. The Nb has been conjugated with the NOTA chelator site-specifically via the Sortase-A enzyme or randomly on its lysines. [68Ga]Ga-NOTA-(hPD-L1) Nbs were obtained in >95% radiochemical purity. In vivo tumor targeting studies at 1 h 20 post-injection revealed specific tumor uptake of 1.89 ± 0.40%IA/g for the site-specific conjugate, 1.77 ± 0.29%IA/g for the random conjugate, no nonspecific organ targeting, and excretion via the kidneys and bladder. Both strategies allowed for easily obtaining 68Ga-labeled hPD-L1 Nbs in high yields. The two conjugates were stable and showed excellent in vivo targeting. Moreover, we proved that the random lysine-conjugation is a valid strategy for clinical translation of the hPD-L1 Nb, despite the lysine present in the CDR.
- Subjects :
- Nanobody
PD-L1
site-specific
PET
gallium-68
Sortase A
Microbiology
QR1-502
Subjects
Details
- Language :
- English
- ISSN :
- 2218273X
- Volume :
- 10
- Issue :
- 10
- Database :
- Directory of Open Access Journals
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0a79df813fc14ca586b2889dfaa8dd9e
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/biom10101388