AI Article Synopsis
- The study evaluates the effectiveness of four types of CD19/CD22 bispecific CAR-T cells to improve treatment outcomes for B-cell tumors, addressing the high relapse rates seen with traditional CD19 CAR-T therapy.
- Researchers compared these CAR-T cell structures based on their cytotoxicity, cytokine secretion, and ability to sustain tumor killing in laboratory settings, as well as in live mouse models.
- Findings reveal that two specific bispecific CAR-T cell structures performed significantly better in controlling tumor growth, even when CD19 levels were low or absent, suggesting a promising new approach to enhancing CAR-T therapy.
Article Abstract
Objectives: 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.
Methods: 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.
Results: 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.
Conclusions: 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).
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| http://dx.doi.org/10.1111/ejh.14090 | DOI Listing |
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