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增强 CAR-T 细胞:在体内白血病模型中经植物血凝素激活释放持久作用潜力

英文原题:Enhancing CAR-T cells: unleashing lasting impact potential with phytohemagglutinin activation in in vivo leukemia model.

PubMed 2023/12/14(内容时间) Cancer Gene Ther Q1 · IF 6.4(JCR 2025)

研究概要

CAR-T(CAR-T)细胞治疗作为一种创新的癌症免疫治疗手段,具有巨大前景。

中文摘要

CAR-T(CAR-T)细胞疗法作为一种创新性癌症免疫治疗方法,具有巨大前景。为优化CAR-T细胞生产和应用,我们评估了不同条件下制备的CAR-T细胞在体内的稳定性和疗效。本研究中,CAR-T细胞分别采用植物血凝素(PHA)或抗CD3和抗CD28进行活化,并在小鼠CD19+B细胞癌模型中比较。结果显示,与抗CD3和抗CD28活化的细胞相比,PHA活化的CAR-T细胞稳定性更高、抗癌疗效更强。具体而言,PHA活化的CAR19BB-T细胞持续增殖并长期存留,同时未损害其抗癌疗效。Kaplan-Meier生存分析显示,与单纯肿瘤组相比,CAR-T治疗组总生存期延长。此外,针对LTR的特异性RT-PCR分析证实治疗组中存在CAR-T细胞,其中CAR19BB-T(PHA)组水平显著高于其他组。脾、肾和肝组织切片的组织病理学分析显示,CAR-T治疗组炎症减轻、组织完整性改善。研究结果突出显示,PHA作为CAR-T细胞制备的共刺激方法可能具有优势,有望增强其稳定性和持久性。这些结果为开发更有效、持久的癌症免疫治疗方法提供了有价值的见解。PHA活化的CAR-T细胞可能成为推动癌症免疫治疗临床应用的有力治疗选择。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunotherapeutic approach for cancer treatment. To optimize the production and application of CAR-T cells, we evaluated the in vivo stability and efficacy capacities of CAR-T cells developed under different conditions. In this study, CAR-T cells were activated using Phytohemagglutinin (PHA) or anti-CD3&anti-CD28 and were compared in an in vivo CD19+B-cell cancer model in mouse groups. Our results demonstrated that CAR-T cells activated with PHA exhibited higher stability and anti-cancer efficacy compared to those activated with anti-CD3&anti-CD28. Specifically, CAR19BB-T cells activated with PHA exhibited continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Kaplan-Meier survival analysis revealed prolonged overall survival in the CAR-T cell-treated groups compared to the only tumor group. Furthermore, specific LTR-targeted RT-PCR analysis confirmed the presence of CAR-T cells in the treated groups, with significantly higher levels observed in the CAR19BB-T (PHA) group compared to other groups. Histopathological analysis of spleen, kidney, and liver tissue sections indicated reduced inflammation and improved tissue integrity in the CAR-T cell-treated groups. Our findings highlight the potential benefits of using PHA as a co-stimulatory method for CAR-T cell production, offering a promising strategy to enhance their stability and persistence. These results provide valuable insights for the development of more effective and enduring immunotherapeutic approaches for cancer treatment. CAR-T cells activated with PHA may offer a compelling therapeutic option for advancing cancer immunotherapy in clinical applications.

论文信息

作者
Sert B、Gulden G、Teymur T、Ay Y、Turan RD、Unaldi OM、Guzenge E、Erdil HE
第一作者单位
Molecular Biology, Institute of Science and Technology, Üsküdar University, Istanbul, Turkey.Turkey
通讯作者单位
Transgenic Cell Technologies and Epigenetic Application and Research Center (TRGENMER), Üsküdar University, Istanbul, Turkey. cihantastan.ct@gmail.com.Turkey
文献类型
非美国政府资助研究
期刊
Cancer gene therapy2024 Mar
原文标识
PubMed 38092962 · DOI 10.1038/s41417-023-00709-9