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首页> 外文期刊>Journal of Reproductive Immunology >Killing cervical cancer cells by specific chimeric antigen receptor-modified T cells
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Killing cervical cancer cells by specific chimeric antigen receptor-modified T cells

机译：通过特异性嵌合抗原受体改性T细胞杀死宫颈癌细胞

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The aim is to investigate the in vivo and in vitro killing effect of mesothelin chimeric antigen receptor T cells (MESO-CAR-T) in cervical squamous cell carcinoma. MESO-CAR-T cells were successfully constructed. In vitro verification of the killing effect of MESO-CAR-T cells was evaluated in the presence of SiHa cells by the lactate dehydrogenase release assay and cytokine release assay. The in vivo experiments were performed in immunodeficient NCG mice. After successful tumor formation with the subcutaneous implantation of SiHa cervical cancer cells, the injections of MESO-CAR-T cells into the tumors at different doses and frequencies were performed. Subsequently, the growth rate and size of the tumors in NCG mice were observed. A 17-fold increase in the number of MESO-CAR-T cells and a 16-fold increase in the number of Con-CAR-T cells were observed. The result of marker detection in the prepared MESO-CAR-T cells showed that CD3(+) T lymphocytes accounted for 97.0 % of all cells, indicating successful preparation of MESO-CAR-T cells. Expression of the membrane protein MESO was detected in 12.8 % of SiHa cells. When the ratio of MESO-CAR-T cells to SiHa cells was 20:1, the lysis of target cells was most significant and was observed in 22 % of the cells. In the presence of SiHa cells, the secretion of IL-4, IL-2, IL-5, TNF-alpha and IFN-gamma in MESO-CAR-T cells was higher than that in the control group. The effect of two consecutive intratumoral injections of MESO-CAR-T cells was more obvious than that of one injection. The pharmacological effect of the injection was observed within 1 week. Our finding identified the certain in vivo and in vitro killing activity of MESO-CAR-T cells.
机译：目的是探讨宫颈嵌合抗原受体T细胞（Meso-Car-T）在宫颈鳞状细胞癌中的体内和体外杀伤作用。成功构建了中草赛COLET细胞。通过乳酸脱氢酶释放测定和细胞因子释放测定，在Siha细胞存在下评估中索-C-T细胞杀伤效果的体外验证。在免疫缺陷小鼠中进行体内实验。在通过皮下植入Siha宫颈癌细胞的皮下植入成功的肿瘤形成后，进行在不同剂量和频率下进入肿瘤中的Meso-Car-T细胞。随后，观察到NCG小鼠中肿瘤的生长速率和大小。观察到Meso-Car-T细胞的数量增加17倍，并且观察到Con-Car-T细胞数量的16倍。制备的中索-CA-T细胞中标记检测结果表明，CD3（+）T淋巴细胞占所有细胞的97.0％，表明中索-CA-T细胞的成功制备。在12.8％的SiHa细胞中检测到膜蛋白质蛋白酶的表达。当Meso-Car-T细胞与Siha细胞的比例为20：1时，靶细胞的裂解最显着，在22％的细胞中观察到。在SiHa细胞存在下，在Meso-Car-T细胞中的IL-4，IL-2，IL-5，TNF-α和IFN-γ的分泌高于对照组中的分泌。连续两个腹腔内注射Meso-Car-T细胞的效果比一次注射更明显。在1周内观察到注射的药理效果。我们的发现鉴定了体内和体外杀伤Meso-Car-T细胞的一定。

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