Enhanced efficacy of CD19/CD22 bispecific CAR-T cells with EAAAK linker on B-cell malignancies.
CAR-T cells
bispecific antibody
immunotherapy
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
06 Sep 2023
06 Sep 2023
Historique:
revised:
12
08
2023
received:
28
05
2023
accepted:
16
08
2023
medline:
6
9
2023
pubmed:
6
9
2023
entrez:
6
9
2023
Statut:
aheadofprint
Résumé
Despite the great success of CD19 CAR-T cell therapy, its clinical efficacy has been greatly hampered by the high relapse rate. In this study, we designed and compared four structures of CD19/CD22 bispecific CAR-T cells with different linkers and different orders of the antibody sequences. We detected the cytotoxicity, cytokine secretion levels, sustainable killing ability, differentiation, exhaustion of these four CAR-T cells in vitro. The optimal Bis-C CAR-T cells were evaluated the efficacy using NSG mice. The two structures of CD19/CD22 bispecific CAR-T cells using (EAAAK)3 as linker had more significant cytotoxicity and cytokine secretion levels. In the process of continuous killing, Bis-C CAR-T cells showed better sustained killing ability, memory phenotype differentiation, and exhaustion. In the in vivo experiment mimicking CD19-negative relapse, Bis-C CAR-T was more able to control the tumor progression of mice in the CD19 low expression or no expression groups than CD19 CAR-T. This study has generated a novel bispecific CAR-T cell that can simultaneously target CD19 or CD22 positive tumor cells, providing a new strategy to address the limitations of single-targeted CAR-T therapy in B-cell tumors (limited response or relapse).
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Key R&D Program of China
ID : 2022YFC2502700
Organisme : Natural Science Foundation of China
ID : 81872431
Organisme : Priority Academic Program Development of Jiangsu Higher Education Institutions, the Collaborative Innovation Major Project
ID : XYXT-2015304
Organisme : Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University
ID : GNZ1201803
Informations de copyright
© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
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