Xiuying Liu , Jingjing Zhu , Jingjing Liu , Yichao Feng , Jiaying Wang , Jianxun Wang
{"title":"Investigating the therapeutic potential of elemene emulsion injection as an adjuvant for chimeric antigen receptor T cell therapy: Transcriptome analysis and experimental validation","authors":"Xiuying Liu , Jingjing Zhu , Jingjing Liu , Yichao Feng , Jiaying Wang , Jianxun Wang","doi":"10.1016/j.eujim.2024.102425","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>in vitro</em>. 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.</div></div><div><h3>Results</h3><div>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+ <em>T</em> 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div><div><h3>Funding</h3><div>Scientific Research Startup Funds for High-level Talents from Beijing University of Chinese Medicine (Grant No. 9,011,451,310,032)</div></div>","PeriodicalId":11932,"journal":{"name":"European Journal of Integrative Medicine","volume":"73 ","pages":"Article 102425"},"PeriodicalIF":1.9000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Integrative Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1876382024000945","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
Investigating the therapeutic potential of elemene emulsion injection as an adjuvant for chimeric antigen receptor T cell therapy: Transcriptome analysis and experimental validation
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)
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.
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