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Anti-human PD-L1 Nanobody for immuno-PET imaging : validation of a conjugation strategy for clinical translation

(2020) BIOMOLECULES. 10(10).
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Organization
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.
Keywords
EXPRESSION, Nanobody, PD-L1, site-specific, PET, gallium-68, Sortase A, cancer

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MLA
Bridoux, Jessica, et al. “Anti-Human PD-L1 Nanobody for Immuno-PET Imaging : Validation of a Conjugation Strategy for Clinical Translation.” BIOMOLECULES, vol. 10, no. 10, 2020, doi:10.3390/biom10101388.
APA
Bridoux, J., Broos, K., Lecocq, Q., Debie, P., Martin, C., Ballet, S., … Xavier, C. (2020). Anti-human PD-L1 Nanobody for immuno-PET imaging : validation of a conjugation strategy for clinical translation. BIOMOLECULES, 10(10). https://doi.org/10.3390/biom10101388
Chicago author-date
Bridoux, Jessica, Katrijn Broos, Quentin Lecocq, Pieterjan Debie, Charlotte Martin, Steven Ballet, Geert Raes, et al. 2020. “Anti-Human PD-L1 Nanobody for Immuno-PET Imaging : Validation of a Conjugation Strategy for Clinical Translation.” BIOMOLECULES 10 (10). https://doi.org/10.3390/biom10101388.
Chicago author-date (all authors)
Bridoux, Jessica, Katrijn Broos, Quentin Lecocq, Pieterjan Debie, Charlotte Martin, Steven Ballet, Geert Raes, Sara Neyt, Christian Vanhove, Karine Breckpot, Nick Devoogdt, Vicky Caveliers, Marleen Keyaerts, and Catarina Xavier. 2020. “Anti-Human PD-L1 Nanobody for Immuno-PET Imaging : Validation of a Conjugation Strategy for Clinical Translation.” BIOMOLECULES 10 (10). doi:10.3390/biom10101388.
Vancouver
1.
Bridoux J, Broos K, Lecocq Q, Debie P, Martin C, Ballet S, et al. Anti-human PD-L1 Nanobody for immuno-PET imaging : validation of a conjugation strategy for clinical translation. BIOMOLECULES. 2020;10(10).
IEEE
[1]
J. Bridoux et al., “Anti-human PD-L1 Nanobody for immuno-PET imaging : validation of a conjugation strategy for clinical translation,” BIOMOLECULES, vol. 10, no. 10, 2020.
@article{8678294,
  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.}},
  articleno    = {{1388}},
  author       = {{Bridoux, Jessica and Broos, Katrijn and Lecocq, Quentin and Debie, Pieterjan and Martin, Charlotte and Ballet, Steven and Raes, Geert and Neyt, Sara and Vanhove, Christian and Breckpot, Karine and Devoogdt, Nick and Caveliers, Vicky and Keyaerts, Marleen and Xavier, Catarina}},
  issn         = {{2218-273X}},
  journal      = {{BIOMOLECULES}},
  keywords     = {{EXPRESSION,Nanobody,PD-L1,site-specific,PET,gallium-68,Sortase A,cancer}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{16}},
  title        = {{Anti-human PD-L1 Nanobody for immuno-PET imaging : validation of a conjugation strategy for clinical translation}},
  url          = {{http://dx.doi.org/10.3390/biom10101388}},
  volume       = {{10}},
  year         = {{2020}},
}

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