CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
IL-24 通过靶向肿瘤细胞干性提高 CAR-T 细胞治疗疗效
英文原题：IL-24 improves efficacy of CAR-T cell therapy by targeting stemness of tumor cells.
查看英文原题
IL-24 improves efficacy of CAR-T cell therapy by targeting stemness of tumor cells.
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研究概要
IL-24 有助于消除 CSCs，并赋予 CAR-T 细胞更强的抗肿瘤反应性。
研究思路结论见上方概要
背景
肿瘤干细胞（CSCs）可诱导治疗耐药，并可能是癌症免疫治疗的重要障碍。CAR-T（CAR-T）细胞疗法在临床环境中已显示出显著疗效。然而，CAR-T 细胞疗法在很大一部分患者中失败，尤其是在实体瘤患者中。目前尚不清楚CSCs如何介导对CAR-T 细胞的耐药，以及CAR-T 细胞能否更有效地清除CSCs。
方法
在本研究中，通过体外和体内实验确定了CSCs对CAR-T 细胞疗法的影响。随后，在T细胞中将Interleukin-24（IL-24）与CAR共同表达。进一步进行了体外和体内实验，以确定IL-24对CSCs和CAR-T 细胞疗法的影响。
结果
IL-24诱导CSCs凋亡，并促进T细胞活化、分化和增殖。CAR.IL-24-T细胞抑制CSC富集，并在体外和体内表现出更强的抗肿瘤活性。
展开英文摘要原文
BACKGROUND
Cancer stem cells (CSCs) induce therapeutic resistance and may be an important barrier to cancer immunotherapy. Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy in clinical settings. However, CAR-T cell therapy fails in a large proportion of patients, especially in those with solid tumors. It is unclear how CSCs mediate resistance to CAR-T cells, and whether CAR-T cells can more effectively eradicate CSCs.
METHODS
In this study, the effect of CSCs on CAR-T cell therapy was determined using in vitro and in vivo assays. Subsequently, Interleukin-24 (IL-24) was expressed along with CAR in T cells. Further in vitro and in vivo tests were performed to determine the effects of IL-24 on CSCs and CAR-T cell therapy.
RESULTS
IL-24 induced apoptosis in CSCs and contributed to T cell activation, differentiation, and proliferation. CAR.IL-24-T cells inhibited CSC enrichment and exhibited stronger antitumor activity in vitro and in vivo.
CONCLUSIONS
IL-24 helps eliminate CSCs and endows CAR-T cells with improved antitumor reactivity.
论文信息
- 作者
- Zhang K、Hu W、Li F、Wen C、Zhou L、Zhang L、Lian J、Liu S
- 第一作者单位
- Biotherapy Center & Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.China
- 通讯作者单位
- Biotherapy Center & Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. yizhang@zzu.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- British journal of cancer2024 May
- 原文标识
- PubMed 38347092 · DOI 10.1038/s41416-024-02601-1
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