Biodistribution of Drug/ADA Complexes: The Impact of Immune Complex Formation on Antibody Distribution.
biodistribution
immune complexes
pharmacokinetics
radiolabeling
tritium
Journal
The AAPS journal
ISSN: 1550-7416
Titre abrégé: AAPS J
Pays: United States
ID NLM: 101223209
Informations de publication
Date de publication:
13 Mar 2024
13 Mar 2024
Historique:
received:
08
12
2023
accepted:
10
02
2024
medline:
13
3
2024
pubmed:
13
3
2024
entrez:
13
3
2024
Statut:
epublish
Résumé
The clinical use of therapeutic monoclonal antibodies (mAbs) for the treatment of cancer, inflammation, and other indications has been successfully established. A critical aspect of drug-antibody pharmacokinetics is immunogenicity, which triggers an immune response via an anti-drug antibody (ADA) and forms drug/ADA immune complexes (ICs). As a consequence, there may be a reduced efficacy upon neutralization by ADA or an accelerated drug clearance. It is therefore important to understand immunogenicity in biological therapies. A drug-like immunoglobulin G (IgG) was radiolabeled with tritium, and ICs were formed using polyclonal ADA, directed against the complementary-determining region of the drug-IgG, to investigate in vivo biodistribution in rodents. It was demonstrated that 65% of the radioactive IC dose was excreted within the first 24 h, compared with only 6% in the control group who received non-complexed
Identifiants
pubmed: 38478197
doi: 10.1208/s12248-024-00899-6
pii: 10.1208/s12248-024-00899-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
33Informations de copyright
© 2024. The Author(s).
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