CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma.
CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma.
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DOI：
10.1186/s12916-023-03040-0
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发表时间：
2023-08-30
期刊：
影响因子：
9.3
通讯作者：
Zhang, Mingzhi
中科院分区：
文献类型：
--
作者：
Li, Hongwen;Song, Wenting;Wu, Jiazhuo;Shi, Zhuangzhuang;Gao, Yuyang;Li, Jiwei;Han, Lijuan;Zhang, Jianxiang;Li, Zhaoming;Li, Yong;Zhang, Mingzhi
自然杀伤/T细胞淋巴瘤（NKTCL）是一种侵袭性淋巴瘤，预后较差。嵌合抗原受体转导T （CAR-T）细胞治疗已成为一种有前途的免疫治疗策略对抗血液系统恶性肿瘤。本研究共生成了4个CAR- t细胞系（CD38-CAR、LMP1-CAR、CD38-LMP1串联CAR- 1和CD38-LMP1串联CAR- 2）。在体内和体外对CAR-T细胞对NKTCL细胞的作用进行了评价。用流式细胞术检测CAR-T细胞产生的T细胞活化标志物和细胞因子的表达。四种CAR-T细胞系均能有效清除恶性NKTCL细胞。它们可以被激活并以靶依赖的方式产生炎症细胞因子。体内实验表明，CAR-T细胞在异种移植的NKTCL小鼠模型中表现出显著的抗肿瘤作用。总之，四种CAR-T细胞系在体外和体内均对NKTCL细胞表现出显著的细胞毒性。这些结果表明CD38和LMP1 CAR-T细胞在NKTCL中的有效治疗前景。在线版本包含补充材料，可在10.1186/s12916-023-03040-0获得。
Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry. The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model. In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL. The online version contains supplementary material available at 10.1186/s12916-023-03040-0.
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影响因子：
7.2
作者：
Feng Y;Liu X;Li X;Zhou Y;Song Z;Zhang J;Shi B;Wang J
通讯作者：
Wang J
影响因子：
3.2
作者：
See HS;Yap YY;Yip WK;Seow HF
通讯作者：
Seow HF
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
DOI：
10.1038/mto.2016.11
发表时间：
2016
期刊：
Molecular therapy oncolytics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.7
作者：
Smatti MK;Al-Sadeq DW;Ali NH;Pintus G;Abou-Saleh H;Nasrallah GK
通讯作者：
Nasrallah GK