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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
XPO1 抑制剂联合 CD19 CAR-T 细胞在 TP53 突变 DLBCL 中的协同效应
英文原题：Synergistic effects of XPO1 inhibitors combined with CD19 CAR-T cells in TP53-mutated DLBCL.
查看英文原题
Synergistic effects of XPO1 inhibitors combined with CD19 CAR-T cells in TP53-mutated DLBCL.
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研究概要
XPO1 抑制剂 KPT-330 通过稳定 p53 和抑制 PI3K-AKT 通路发挥抗癌作用，为弥漫大 B 细胞淋巴瘤的治疗提供了分子基础。
中文摘要
方法
采用qRT-PCR、Western blot、CCK8和流式细胞术研究XPO1与突变型p53的相关性，并使用XPO1抑制剂KPT-330评估其对DLBCL细胞凋亡的作用。TCGA数据库分析显示，XPO1相关基因与PI3K-AKT通路存在明确关联。
结果
XPO1抑制剂KPT-330与CAR-T 联合，可协同降低DLBCL细胞活性并增强CAR-T 杀伤作用。正如预期，KPT-330联合CAR-T 减缓p53突变型DLBCL肿瘤生长并降低肿瘤负荷。机制上，KPT-330可通过激活PI3K通路与CAR-T 协同治疗DLBCL。体外细胞毒性实验进一步显示，联合组显著增强效应细胞因子IFN-γ、TNF-α和IL-2分泌，并激活免疫系统。
结论
XPO1抑制剂KPT-330通过稳定p53并抑制PI3K-AKT通路发挥抗癌作用，为DLBCL治疗提供分子依据。该联合疗法可能成为治疗p53突变型DLBCL的有前景方案。
展开英文摘要原文
METHODS
We investigated the correlation between XPO1 and mut-P53 employing qRT-PCR, WB, CCK8 and flow cytometry. Then, we conduct XPO1 inhibitor (KPT-330) to explore the apoptotic effect on DLBCL. Through the TCGA database, there is a clear correlation between XPO1-related genes and the PI3K-AKT pathway.
RESULTS
In this study, we showed that XPO1 inhibitor (KPT-330) synergized with CAR-T to reduce the viability of DLBCL and enhance the killing effect of CAR-T cells. As expected, KPT-330 combined with CAR-T therapy slowed tumor growth and reduced tumor burden in DLBCL with p53 mutations. Mechanistically, XPO1 inhibitor KPT-330 can cooperate with CAR-T in the treatment of DLBCL by activating the PI3K pathway. Then, in vitro cytotoxicity assays revealed that the KPT-330 combined with CAR-T group significantly enhanced the secretion of effector cytokines IFN- , TNF- , and IL-2, and activated the immune system.
CONCLUSIONS
The XPO1 inhibitor KPT-330 exerts anti-cancer effects through stabilizing p53 and inhibiting the PI3K-AKT pathway, providing a molecular basis for DLBCL treatment. We may provide a potential promising combination therapy for the treatment of DLBCL with p53 mutations.
论文信息
- 作者
- Bai Z、Huang X、Wang X、Zhou Y、Lin Z、Liu H
- 单位
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong China.China
- 期刊
- Tumori2026 Jun
- 原文标识
- PubMed 41498261 · DOI 10.1177/03008916251408273