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CAR-T 细胞对改造实体瘤细胞系的细胞毒性评估

英文原题:Evaluation of CAR-T Cells' Cytotoxicity against Modified Solid Tumor Cell Lines.

PubMed 2023/02/19(内容时间) Biomedicines Q2 · IF 4.5(JCR 2025)

研究概要

近年来,由于技术的发展以及 CAR-T 细胞成功用于恶性 B 细胞肿瘤患者的临床治疗,过继细胞疗法获得了新的应用前景。

中文摘要

近年来,随着CAR-T细胞技术的发展及其成功应用于恶性B细胞肿瘤患者的临床治疗,过继细胞疗法的应用前景得到新的拓展。然而,CAR-T治疗实体瘤的疗效仍是重大的科学和临床挑战。本研究评估了第二代CAR-T细胞对经改造实体瘤细胞系的细胞毒作用。这些细胞系包括肺腺癌H522、前列腺癌PC-3M、乳腺癌MDA-MB-231和表皮样癌A431,并经慢病毒转导表达红色荧光蛋白Katushka2S和CD19抗原。结果显示,促炎细胞因子分泌增加与肿瘤细胞单层融合度下降相关。所提出的方法有望用于初步评估CAR-T细胞治疗实体瘤的疗效,并估计发生细胞因子释放综合征的风险。

展开英文摘要原文

In recent years, adoptive cell therapy has gained a new perspective of application due to the development of technologies and the successful clinical use of CAR-T cells for the treatment of patients with malignant B-cell neoplasms. However, the efficacy of CAR-T therapy against solid tumor remains a major scientific and clinical challenge. In this work, we evaluated the cytotoxicity of 2nd generation CAR-T cells against modified solid tumors cell lines-lung adenocarcinoma cell line H522, prostate carcinoma PC-3M, breast carcinoma MDA-MB-231, and epidermoid carcinoma A431 cell lines transduced with lentiviruses encoding red fluorescent protein Katushka2S and the CD19 antigen. A correlation was demonstrated between an increase in the secretion of proinflammatory cytokines and a decrease in the confluence of tumor cells' monolayer. The proposed approach can potentially be applied to preliminarily assess CAR-T cell efficacy for the treatment of solid tumors and estimate the risks of developing cytokine release syndrome.

论文信息

作者
Valiullina AK、Zmievskaya EA、Ganeeva IA、Zhuravleva MN、Garanina EE、Rizvanov AA、Petukhov AV、Bulatov ER
单位
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.Russia
期刊
Biomedicines2023 Feb 19
原文标识
PubMed 36831162 · DOI 10.3390/biomedicines11020626