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Anti-human PD-L1 Nanobody for Immuno-PET Imaging

Journal Contribution - Journal Article

Subtitle:Validation of a Conjugation Strategy for Clinical Translation

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.

Journal: Biomolecules
ISSN: 2218-273X
Issue: 10
Volume: 10
Pages: 1-15
Publication year:2020
  • WoS Id: 000584174700001
  • ORCID: /0000-0001-9220-4833/work/88545703
  • ORCID: /0000-0002-4301-5902/work/82020942
  • ORCID: /0000-0002-8895-9763/work/82019580
  • ORCID: /0000-0002-2627-0880/work/82019517
  • ORCID: /0000-0002-9128-7814/work/82019449
  • ORCID: /0000-0002-9997-4571/work/82019087
  • ORCID: /0000-0002-9065-1549/work/82018988
  • ORCID: /0000-0001-7368-9142/work/82018847
  • ORCID: /0000-0001-9006-1074/work/82018535
  • Scopus Id: 85091750058
  • DOI: https://doi.org/10.3390/biom10101388
  • Institutional Repository URL: https://cris.vub.be/ws/files/69951891/Bridoux_Biomolecules_2021.pdf
CSS-citation score:1