Cellular kinetics: A clinical and computational review of CAR-T cell pharmacology.
CAR-T cells
Cancer immunology
Immunotherapy
Lymphocyte trafficking
Mathematical modeling
Translational science
Journal
Advanced drug delivery reviews
ISSN: 1872-8294
Titre abrégé: Adv Drug Deliv Rev
Pays: Netherlands
ID NLM: 8710523
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
17
02
2022
revised:
28
06
2022
accepted:
04
07
2022
pubmed:
10
7
2022
medline:
17
8
2022
entrez:
9
7
2022
Statut:
ppublish
Résumé
To the extent that pharmacokinetics influence the effectiveness of nonliving therapeutics, so too do cellular kinetics influence the efficacy of Chimeric Antigen Receptor (CAR) -T cell therapy. Like conventional therapeutics, CAR-T cell therapies undergo a distribution phase upon administration. Unlike other therapeutics, however, this distribution phase is followed by subsequent phases of expansion, contraction, and persistence. The magnitude and duration of these phases unequivocally influence clinical outcomes. Furthermore, the "pharmacodynamics" of CAR-T cells is truly dynamic, as cells can rapidly become exhausted and lose their therapeutic efficacy. Mathematical models are among the translational tools commonly applied to assess, characterize, and predict the complex cellular kinetics and dynamics of CAR-T cells. Here, we provide a focused review of the cellular kinetics of CAR-T cells, the mechanisms underpinning their complexity, and the mathematical modeling approaches used to interrogate them.
Identifiants
pubmed: 35809868
pii: S0169-409X(22)00311-8
doi: 10.1016/j.addr.2022.114421
pmc: PMC9520251
mid: NIHMS1837115
pii:
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
114421Subventions
Organisme : NCI NIH HHS
ID : R01 CA256898
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA211056
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA243543
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA247436
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119661
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T.Q. is a contractor for Hatteras Venture Partners. Y.C. is a consultant for Janssen Research & Development. G.D. has patents related to the generation of CAR molecules. G.D. is a paid consultant for Bellicum Pharmaceuticals, Tessa Therapeutics, and Catamaran.
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