顺铂
癌症干细胞
癌症研究
干细胞
嵌合抗原受体
单元格排序
癌细胞
医学
癌症
细胞因子
化学
细胞毒性
CD44细胞
流式细胞术
细胞毒性T细胞
免疫学
边居
生物
免疫疗法
化疗
内科学
体外
细胞生物学
生物化学
作者
Yang Han,Bo Sun,Hong Cai,Yi Xuan
标识
DOI:10.1007/s00262-021-02891-x
摘要
CD133 + cancer stem cells mediate chemoresistance in multiple aggressive cancers, and anti-CD133 chimeric antigen receptor T (CAR-T) cells are designed to selectively target cisplatin-resistant gastric cancer stem cells in this investigation. The relative CD133 expression was detected in gastric cancer patients before and after cisplatin treatment. Anti-CD133 CAR-T cells were incubated with cisplatin-exposed CD133+ BGC-823 cells to evaluate the killing efficacy. At the same time, the canonical T cell activation markers were assayed by fluorescence-activated cell sorting, and the functional cytokine profile was detected with enzyme-linked immunosorbent assays. In addition to the percentage of CD133 positive stem cell-like cells, the volume and weight of subcutaneous tumors in BGC-823, KATO III and MKN-28 xenograft models were measured to evaluate the anti-tumor activity of cisplatin and anti-CD133 CAR-T combination strategy. After cisplatin treatment, both human samples and BGC-823 cells showed up-regulated CD133 expression. Anti-CD133 CAR-T cells exhibited pronounced killing efficiency against cisplatin-exposed CD133+ BGC-823 cells with up-regulated activation markers and cytotoxicity cytokine production. Moreover, cisplatin and anti-CD133 CAR-T combination treatment inhibited tumor progression in three different xenograft models with diminished CD133 positive stem cell-like cell infiltration. These results indicate that cisplatin and anti-CD133 CAR-T combination strategy can simultaneously target normal and stem cell-like gastric cancer cells to improve the treatment outcome.
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