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DC 疫苗通过克服 T 细胞耗竭与促进 T 细胞浸润增强实体瘤中 CAR-T 细胞抗肿瘤活性

英文原题:DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors.

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DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors.

PubMed 2023/04/20(内容时间) Clin Transl Oncol Q3 · IF 2.7(JCR 2025)

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研究概要

本研究表明,DC 疫苗可促进 CAR-T 疗法在实体瘤中的效果,这为未来 CAR-T 细胞的广泛临床应用提供了可能。

中文摘要

CAR-T 细胞免疫疗法治疗血液系统肿瘤取得巨大成功,但治疗实体瘤尤其困难,因为 CAR-T 难以进入肿瘤内部并产生长期稳定的免疫效应。树突状细胞(DC)既可呈递肿瘤抗原,又可促进 T 细胞浸润。因此,借助 DC 疫苗增强 CAR-T 可能是治疗实体瘤的可靠策略。

为检验 DC 疫苗能否促进 CAR-T 治疗实体瘤,将 DC 疫苗与 MSLN CAR-T 细胞共培养,通过测量细胞增殖、分化和细胞因子分泌评估 DC 疫苗对 CAR-T 的体外作用。使用皮下荷瘤小鼠评估 DC 疫苗的体内作用,通过免疫荧光分析 CAR-T 浸润,并以实时定量 PCR 分析小鼠血液中 CAR-T 的持续存在。

DC 疫苗显著增强 MSLN CAR-T 细胞体外增殖潜力;不仅促进 CAR-T 细胞浸润,也显著提高其在体内实体瘤中的持续存在能力。

本研究证明 DC 疫苗可促进 CAR-T 治疗实体瘤,为未来 CAR-T 细胞的广泛临床应用提供了可能。

展开英文摘要原文

Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors.

To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR.

The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo.

In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future.

论文信息

作者
Zhang M、Wang Y、Chen X、Zhang F、Chen J、Zhu H、Li J、Chen Z
第一作者单位
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China.China
通讯作者单位
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. lfhe22@139.com.China
期刊
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2023 Oct
原文标识
PubMed 37079211 · DOI 10.1007/s12094-023-03161-1