Anti-Tumor Efficacy of PD-L1 Targeted Alpha-Particle Therapy in a Human Melanoma Xenograft Model - Archive ouverte HAL Access content directly
Journal Articles Cancers Year : 2021

Anti-Tumor Efficacy of PD-L1 Targeted Alpha-Particle Therapy in a Human Melanoma Xenograft Model

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Marisa Capitao
  • Function : Author
  • PersonId : 1093733
Justine Perrin
  • Function : Author
  • PersonId : 1093734
Sébastien Gouard
  • Function : Author
  • PersonId : 1093736
Nicolas Chouin
  • Function : Author
  • PersonId : 1093737
Latifa Rbah-Vidal
Yannick Guilloux
  • Function : Author
  • PersonId : 995952
Joëlle Gaschet
  • Function : Author
  • PersonId : 910960

Abstract

PD-L1 (programmed death-ligand 1, B7-H1, CD274), the ligand for PD-1 inhibitory receptor, is expressed on various tumors, and its expression is correlated with a poor prognosis in melanoma. Anti-PD-L1 mAbs have been developed along with anti-CTLA-4 and anti-PD-1 antibodies for immune checkpoint inhibitor (ICI) therapy, and anti-PD-1 mAbs are now used as first line treatment in melanoma. However, many patients do not respond to ICI therapies, and therefore new treatment alternatives should be developed. Because of its expression on the tumor cells and on immunosuppressive cells within the tumor microenvironment, PD-L1 represents an interesting target for targeted alpha-particle therapy (TAT). We developed a TAT approach in a human melanoma xenograft model that stably expresses PD-L1 using a 213Bi-anti-human-PD-L1 mAb. Unlike treatment with unlabeled anti-human-PD-L1 mAb, TAT targeting PD-L1 significantly delayed melanoma tumor growth and improved animal survival. A slight decrease in platelets was observed, but no toxicity on red blood cells, bone marrow, liver or kidney was induced. Anti-tumor efficacy was associated with specific tumor targeting since no therapeutic effect was observed in animals bearing PD-L1 negative melanoma tumors. This study demonstrates that anti-PD-L1 antibodies may be used efficiently for TAT treatment in melanoma.
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Dates and versions

inserm-03171640 , version 1 (17-03-2021)

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Marisa Capitao, Justine Perrin, Sylvain Simon, Sébastien Gouard, Nicolas Chouin, et al.. Anti-Tumor Efficacy of PD-L1 Targeted Alpha-Particle Therapy in a Human Melanoma Xenograft Model. Cancers, 2021, 13 (6), pp.1256. ⟨10.3390/cancers13061256⟩. ⟨inserm-03171640⟩
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