Anti-Tumor Efficacy of PD-L1 Targeted Alpha-Particle Therapy in a Human Melanoma Xenograft Model - Institut de cancérologie de l'Ouest Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2021

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

Marisa Capitao
  • Fonction : Auteur
  • PersonId : 1093733
Justine Perrin
  • Fonction : Auteur
  • PersonId : 1093734
Sylvain Simon
  • Fonction : Auteur
  • PersonId : 1093735
Sébastien Gouard
  • Fonction : Auteur
  • PersonId : 1093736
Nicolas Chouin
Latifa Rbah-Vidal
Yannick Guilloux
  • Fonction : Auteur
  • PersonId : 995952
Joëlle Gaschet
  • Fonction : Auteur
  • PersonId : 910960

Résumé

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.

Domaines

Cancer
Fichier principal
Vignette du fichier
Capitao2021Eq13.pdf (3.41 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

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

Identifiants

Citer

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⟩
150 Consultations
77 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More