Best practices for optimization and validation of flow cytometry-based receptor occupancy assays.
drug development
flow cytometry
immunotherapeutics
receptor occupancy
validation
Journal
Cytometry. Part B, Clinical cytometry
ISSN: 1552-4957
Titre abrégé: Cytometry B Clin Cytom
Pays: United States
ID NLM: 101235690
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
22
06
2020
revised:
16
09
2020
accepted:
15
10
2020
pubmed:
2
12
2020
medline:
27
1
2022
entrez:
1
12
2020
Statut:
ppublish
Résumé
In the development of therapeutic compounds that bind cell surface molecules, it is critical to demonstrate the extent to which the drug engages its target. For cell-associated targets, flow cytometry is well-suited to monitor drug-to-target engagement through receptor occupancy assays (ROA). The technology allows for the identification of specific cell subsets within heterogeneous populations and the detection of nonabundant cellular antigens. There are numerous challenges in the design, development, and implementation of robust ROA. Among the most difficult challenges are situations where there is receptor modulation or when the target-antigen is expressed at low levels. When the therapeutic molecules are bi-specific and bind multiple targets, these challenges are increased. This manuscript discusses the challenges and proposes best practices for designing, optimizing, and validating ROA.
Identifiants
pubmed: 33259706
doi: 10.1002/cyto.b.21970
doi:
Substances chimiques
Pharmaceutical Preparations
0
Receptors, Fc
0
Types de publication
Journal Article
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
63-71Informations de copyright
© 2020 International Clinical Cytometry Society.
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