Fc-engineered monoclonal antibodies to reduce off-target liver uptake - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue EJNMMI Research Année : 2023

Fc-engineered monoclonal antibodies to reduce off-target liver uptake

Résumé

Background Radiolabeled-antibodies usually display non-specific liver accumulation that may impair image analysis and antibody biodistribution. Here, we investigated whether Fc silencing influenced antibody biodistribution. We compared recombinant 89 Zr-labeled antibodies (human IgG1 against different targets) with wild-type Fc and with mutated Fc (LALAPG triple mutation to prevent binding to Fc gamma receptors; FcγR). After antibody injection in mice harboring xenografts of different tumor cell lines or of immortalized human myoblasts, we analyzed antibody biodistribution by PET-CT and conventional biodistribution analysis. Results Accumulation in liver was strongly reduced and tumor-specific targeting was increased for the antibodies with mutated Fc compared with wild-type Fc. Conclusion Antibodies with reduced binding to FcγR display lower liver accumulation and better tumor-to-liver ratios. These findings need to be taken into account to improve antibody-based theragnostic approaches.
Fichier principal
Vignette du fichier
s13550-023-01030-0.pdf (1.17 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Licence

Dates et versions

hal-04598633 , version 1 (03-06-2024)

Licence

Identifiants

Citer

Tristan Mangeat, Matthieu Gracia, Alexandre Pichard, Sophie Poty, Pierre Martineau, et al.. Fc-engineered monoclonal antibodies to reduce off-target liver uptake. EJNMMI Research, 2023, 13 (1), pp.81. ⟨10.1186/s13550-023-01030-0⟩. ⟨hal-04598633⟩
16 Consultations
2 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More