Investigating the therapeutic potential of elemene emulsion injection as an adjuvant for chimeric antigen receptor T cell therapy: Transcriptome analysis and experimental validation

IF 1.9 4区医学 Q3 INTEGRATIVE & COMPLEMENTARY MEDICINE

European Journal of Integrative Medicine Pub Date : 2025-01-01 DOI:10.1016/j.eujim.2024.102425

Xiuying Liu , Jingjing Zhu , Jingjing Liu , Yichao Feng , Jiaying Wang , Jianxun Wang

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引用次数: 0

Abstract

Introduction

Elemene emulsion injection (EEI) is prepared from monomers extracted from Chinese medicine. It has been used as an adjuvant anti-tumor medication in clinical settings for over 30 years. Chimeric antigen receptor T cells (CAR-T) are a successful immunotherapy strategy for tumor treatment. This study aimed to investigate the role and potential mechanisms of EEI as an adjuvant to CAR-T cells for tumor treatment.

Methods

CCK8 staining was utilized to detect the effect of EEI on tumor cell viability. CD19 CAR-T and Trop2 CAR-T cells were constructed, and EEI was added to the experimental system. Untreated CAR-T cells served as a control group. After co-culture with tumor cells, the effect of EEI on CAR-T cell function was assessed. Flow cytometry, luciferase reporter gene, IncuCyte, and cytokine assays were used to evaluate the effects of the EEI on CAR-T cell cytotoxicity and phenotype in vitro. RNA sequencing was utilized to analyze the effect of EEI on CAR-T cell gene expression. Network pharmacology was applied to predict potential EEI therapeutic targets for CRS, which were verified via a THP-1 macrophage inflammation model.

Results

EEI enhanced the cytotoxicity of CAR-T cells against tumors. RNA-seq revealed that EEI modulated cytokine activity and Th17 cell differentiation in CAR-T cells. Subsequent experiments confirmed that the proportion of CD4+ T cells in CAR-T cells increased. The secretion of cytokines was greatly reduced under the effect of EEI. In the THP-1 macrophage inflammation model, EEI significantly reduced the levels of cytokines associated with inflammation induced by CAR-T cells.

Conclusions

This research proposed and tested a combination therapy involving EEI and CAR-T cells. The combination of CAR-T cells with EEI for tumor immunotherapy may enhance the clinical efficacy while providing synergistic effects and reducing toxicity.

Funding

Scientific Research Startup Funds for High-level Talents from Beijing University of Chinese Medicine (Grant No. 9,011,451,310,032)

Abstract Image

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导言爱尔蒙乳液注射液（EEI）由从中药中提取的单体制备而成。30 多年来，它一直被用作临床抗肿瘤的辅助药物。嵌合抗原受体 T 细胞（CAR-T）是一种成功的肿瘤免疫治疗策略。本研究旨在探讨 EEI 作为 CAR-T 细胞治疗肿瘤的辅助药物的作用和潜在机制。构建 CD19 CAR-T 细胞和 Trop2 CAR-T 细胞，并在实验系统中加入 EEI。未经处理的 CAR-T 细胞作为对照组。与肿瘤细胞共培养后，评估 EEI 对 CAR-T 细胞功能的影响。使用流式细胞术、荧光素酶报告基因、IncuCyte 和细胞因子检测来评估 EEI 对体外 CAR-T 细胞细胞毒性和表型的影响。利用 RNA 测序分析了 EEI 对 CAR-T 细胞基因表达的影响。结果EEI增强了CAR-T细胞对肿瘤的细胞毒性。RNA-seq显示，EEI调节了CAR-T细胞的细胞因子活性和Th17细胞分化。随后的实验证实，CAR-T 细胞中 CD4+ T 细胞的比例增加了。在 EEI 的作用下，细胞因子的分泌大大减少。在 THP-1 巨噬细胞炎症模型中，EEI 能显著降低 CAR-T 细胞诱导的炎症相关细胞因子的水平。基金项目北京中医药大学高层次人才科研启动基金（批准号：9011,451,310,032）。

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来源期刊

European Journal of Integrative Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-

CiteScore

4.70

自引率

4.00%

发文量

102

审稿时长

33 days

期刊介绍： The European Journal of Integrative Medicine (EuJIM) considers manuscripts from a wide range of complementary and integrative health care disciplines, with a particular focus on whole systems approaches, public health, self management and traditional medical systems. The journal strives to connect conventional medicine and evidence based complementary medicine. We encourage submissions reporting research with relevance for integrative clinical practice and interprofessional education. EuJIM aims to be of interest to both conventional and integrative audiences, including healthcare practitioners, researchers, health care organisations, educationalists, and all those who seek objective and critical information on integrative medicine. To achieve this aim EuJIM provides an innovative international and interdisciplinary platform linking researchers and clinicians. The journal focuses primarily on original research articles including systematic reviews, randomized controlled trials, other clinical studies, qualitative, observational and epidemiological studies. In addition we welcome short reviews, opinion articles and contributions relating to health services and policy, health economics and psychology.