不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
泽布替尼联合 CD19 CAR-T 细胞在体外和体内 Raji 细胞中的协同效应
英文原题：Synergistic Effects of Zanubrutinib Combined With CD19 CAR-T Cells in Raji Cells in Vitro and in Vivo.
查看英文原题
Synergistic Effects of Zanubrutinib Combined With CD19 CAR-T Cells in Raji Cells in Vitro and in Vivo.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
背景与目的
Bruton酪氨酸激酶抑制剂常用于治疗淋巴瘤和慢性淋巴细胞白血病（CLL）且有效。伊布替尼可能提高抗分化簇19（CD19）嵌合抗原受体（CD19 CAR）T细胞疗法在淋巴瘤中的效果，但泽布替尼联合CAR-T 细胞的效果尚不清楚。
方法
我们选择低效靶比（E:T = 1:3）在体外研究这种协同效应。通过流式细胞术（FCM）分析CD19 CAR-T 细胞中程序性细胞死亡蛋白1（PD-1）的表达以及T淋巴细胞的免疫表型。我们选择一名弥漫性大B细胞淋巴瘤（DLBCL）患者的CD19 CAR-T 细胞，通过生物发光成像监测研究泽布替尼与CAR-T 细胞的协同效应。通过FCM比较小鼠体内CD19 CAR-T 细胞的扩增。
结果
泽布替尼和伊布替尼对CAR-T 细胞和淋巴瘤细胞均具有剂量依赖性毒性。但在体外，CD19 CAR-T 细胞联合泽布替尼/伊布替尼没有显著的协同效应。当CD19 CAR-T 细胞与Raji细胞共培养时，CD19 CAR-T 细胞中PD-1表达增加，而在培养中加入伊布替尼时PD-1表达降低，但泽布替尼没有这种效应。伊布替尼联合CD19 CAR-T 细胞联合治疗组的荧光素酶表达消失比其他组更明显。此外，CD19 CAR-T 细胞联合伊布替尼治疗组中CAR-T 细胞的比例高于CD19 CAR-T 细胞联合泽布替尼联合治疗组。在接受伊布替尼联合CD19 CAR-T 细胞的小鼠中可明显观察到协同效应。但zanubrutinib在体外或小鼠体内均不能发挥联合治疗效应。
结论
zanubrutinib在体外和小鼠体内均可能与CD19 CAR-T 细胞无联合治疗效应，但不同疗效的机制需要我们进一步研究和探索。
展开英文摘要原文
Background and Objects: Bruton's tyrosine kinase inhibitors are commonly used and effective for lymphoma and chronic lymphocytic leukemia (CLL). Ibrutinib might improve the effect of anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CD19 CAR) T-cell therapy in lymphoma, but the effects of zanubrutinib combined with CAR-T cells is unclear.
Methods: We selected a low effect-target ratio (E:T = 1:3) to study this synergistic effect in vitro. The programed cell death protein 1 (PD-1) expression in CD19 CAR-T cells and immune phenotype of T lymphocytes were analyzed by flow cytometry (FCM).
We selected CD19 CAR-T cells of a patient with diffuse large B cell lymphoma (DLBCL) to study the synergistic effect of zanubrutinib with CAR-T cells by bioluminescence imaging monitoring. The CD19 CAR-T cells expansion in mice was compared by FCM. Results: Zanubrutinib and ibrutinib had dose-dependent toxicity on both CAR-T cells and lymphoma cells.
But there was no significant synergistic effect of the CD19 CAR-T cells combined with zanubrutinib/ibrutinib in vitro. The PD-1 expression in CD19 CAR-T cells increased when the CD19 CAR-T cells were co-cultured with Raji cells and decreased when ibrutinib was added in culture, but zanubrutinib had no such effect. The extinction of luciferase expression was more obvious in the polytherapy group of ibrutinib and CD19 CAR-T cell than that in the other groups.
Moreover, the proportion of CAR-T cells in the combination therapy group of CD19 CAR-T cells and ibrutinib was higher than that of the polytherapy group of CD19 CAR-T cells with zanubrutinib group. The synergistic effect could be observed obviously in mice receiving ibrutinib combined with CD19 CAR-T cells.
But zanubrutinib cannot perform joint therapy effect either in vitro or in mice. Conclusion: Zanubrutinib might have no joint therapy effect with CD19 CAR-T cells neither in vitro nor in mice, but the mechanism of different curative effects requires our further research and exploration.
论文信息
- 作者
- Ye X、Liu M、Lv C、Li Y、Chen L、Zhang J、Mu J、Deng Q
- 第一作者单位
- 159438People's Hospital of Ningxia Hui Autonomous Region, Yinchuan City, China.China
- 通讯作者单位
- Department of Hematology, 66571Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Technology in cancer research & treatment2022 Jan-Dec
- 原文标识
- PubMed 36254554 · DOI 10.1177/15330338221133224
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →