Monitoring CAR-T cell kinetics in clinical trials by multiparametric flow cytometry: Benefits and challenges.
CAR-T
cellular kinetics
critical reagents
flow cytometry
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:
04
12
2019
revised:
04
05
2020
accepted:
08
05
2020
pubmed:
24
6
2020
medline:
27
1
2022
entrez:
24
6
2020
Statut:
ppublish
Résumé
Exceptional clinical responses produced by the first chimeric antigen receptor T [CAR-T] cell therapies, and their entry into commercial markets prompted a logarithmic increase in the number of next generation CAR-T clinical trials. As a result, there is a growing interest in understanding the analytical approaches utilized for reliable monitoring of these "living" drugs, and the challenges encountered during their clinical development. Multiparametric flow cytometry (MFC) assays have played a crucial role in understanding the phenotype and function of first approved CAR-T therapies. Herein, three main areas for monitoring CAR-T therapies in clinical trials are discussed: (1) analytical considerations critical for development of MFC assays for the reliable enumeration of CAR-T levels, (2) operational challenges associated with clinical trial sampling and transportation, and (3) differential cellular kinetics observed by MFC and qPCR analyses and their relationship with efficacy (measurable residual disease levels). Initial experiences described here may enable design of fit-for-purpose tools and help to more rapidly advance the development of next generation CAR-T therapies.
Identifiants
pubmed: 32573972
doi: 10.1002/cyto.b.21891
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
72-78Informations de copyright
© 2020 International Clinical Cytometry Society.
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