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Updated: Jan 14, 2026
Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
In vitro study on reversible regulation of CAR-T function by Kinsenoside
Guangmei Li1,2, Delian Zhou1,2, Shangwu Ning3
1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Backgrounds:
Chimeric antigen receptor T-cell (CAR-T) therapy has effectively treated various types of malignant tumors. However, effective methods to address its excessive expansion are currently lacking.
Aims:
We aimed to identify a natural compound that can safely and reversibly regulate CAR-T cell function.
Materials And Methods:
This study combined virtual screening of network pharmacology with in vitro experimental verification to evaluate how a natural small-molecule kinsenoside (KD) can dynamically regulate the function of CAR-T cells. Human and CAR-T cells were treated with KD. Following the intervention and subsequent drug withdrawal, we conducted flow cytometry for T-cell functional tests, such as cell proliferation, cell cycle, and cytotoxicity. Additionally, transcriptome analysis was used to investigate the potential regulatory mechanisms involved.
Results:
The results indicated that KD inhibited CAR-T cell proliferation, blocked the cell cycle, reduced the killing function, and reduced IL6 secretion. KD drives CAR-T cells to Th17 fate without shifting CD4+/CD8 + ratios, modulating inflammation via Th17 pathways. The drug exhibits excellent characteristics, such as good reversibility, controllability, and low toxicity.
Conclusions:
Thus, this natural occurring small molecule can act as a "functional switch," thereby providing new ideas for the balance between toxicity management and the efficacy of CAR-T therapy. Furthermore, it has the potential to pave the way for the combination of traditional Chinese medicine and modern cell therapy technology.
Insights
A novel natural compound, kinsenoside (KD), acts as a functional switch to safely control chimeric antigen receptor T-cell (CAR-T) therapy. This discovery offers a new method for balancing CAR-T efficacy and managing toxicity.
Area of Science:
- Immunotherapy
- Cellular Therapy
- Pharmacology
Background:
- Chimeric antigen receptor T-cell (CAR-T) therapy shows promise in treating cancers.
- Current limitations include a lack of methods to control excessive CAR-T cell expansion and associated toxicities.
Purpose of the Study:
- To identify a natural compound capable of safely and reversibly regulating CAR-T cell function.
- To investigate kinsenoside (KD) as a potential regulator of CAR-T cell activity.
Main Methods:
- Combined virtual screening via network pharmacology with in vitro experimental validation.
- Treated human and CAR-T cells with KD, followed by drug withdrawal.
- Utilized flow cytometry for functional assays (proliferation, cell cycle, cytotoxicity) and transcriptome analysis to explore mechanisms.
Main Results:
- KD inhibited CAR-T cell proliferation, cell cycle progression, and cytotoxicity, while reducing IL-6 secretion.
- KD induced a Th17 cell fate in CAR-T cells, modulating inflammation via Th17 pathways without altering CD4+/CD8+ ratios.
- KD demonstrated good reversibility, controllability, and low toxicity.
Conclusions:
- Kinsenoside functions as a controllable "functional switch" for CAR-T cells.
- This offers a novel strategy for balancing CAR-T therapy efficacy with toxicity management.
- Highlights the potential integration of traditional Chinese medicine with modern cell therapy.
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