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多细胞肿瘤-基质球(CSS)用于 CAR-T 细胞相关毒性的体外评估

英文原题:Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity.

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Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity.

PubMed 2024/11/16(内容时间) Cells Q2 · IF 6(JCR 2025)

研究概要

CAR-T 治疗彻底改变了肿瘤学领域,为癌症患者提供了一种有前景的治疗选择。

中文摘要

CAR-T疗法推动了肿瘤学领域变革,为癌症患者提供了有前景的治疗选择。然而,治疗相关毒性造成的显著发病负担,仍是其广泛应用的主要挑战。尽管CAR-T治疗相关毒性的机制已得到大量研究,仍有许多问题尚未明确。此外,缺乏适当的体外模型来评估免疫毒性和神经毒性,也进一步增加了开发更安全细胞疗法的难度。此前,研究者已在实验室建立由前列腺腺癌PC3细胞和间充质干细胞(MSC)组成的癌症-基质球体(CSS)。本研究提供证据,表明多细胞CSS可作为CAR-T治疗相关毒性研究的有用体外模型。与由单一细胞类型构成的球体相比,含有CD19过表达PC3M细胞的CSS在存在抗CD19 CAR-T细胞时,会分泌更多与CAR-T毒性相关的IL-8、MCP-1和IP-10。

展开英文摘要原文

CAR-T therapy has revolutionized the field of oncology, offering a promising treatment option for cancer patients. However, the significant morbidity associated with therapy-related toxicity presents a major challenge to its widespread use. Despite extensive research into the underlying mechanisms of CAR-T therapy-related toxicity, there are still many unknowns. Furthermore, the lack of adequate in vitro models for assessing immunotoxicity and neurotoxicity further complicates the development of safer cellular therapies. Previously in our laboratory, we developed cancer-stroma spheres (CSS) composed of prostate adenocarcinoma PC3 cells and mesenchymal stem cells (MSC). Herein we present evidence that multicellular CSS could serve as a valuable in vitro model for toxicity studies related to CAR-T therapy. CSS containing CD19-overexpressing PC3M cells exhibited increased secretion of CAR-T cell toxicity-associated IL-8, MCP-1, and IP-10 in the presence of anti-CD19 CAR-T cells, compared to spheres derived from single cell types.

论文信息

作者
Rakhmatullina AR、Zolotykh MA、Filina YV、Valiullina AK、Zmievskaya EA、Gafurbaeva DU、Sagdeeva AR、Bulatov ER
单位
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.Russia
文献类型
非美国政府资助研究
期刊
Cells2024 Nov 16
原文标识
PubMed 39594640 · DOI 10.3390/cells13221892