Chimeric CTLA4-CD28-CD3z T Cells Potentiate Antitumor Activity Against CD80/CD86-Positive B Cell Malignancies.
Chimeric CTLA4-CD28-CD3z T Cells Potentiate Antitumor Activity Against CD80/CD86-Positive B Cell Malignancies.
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嵌合 CTLA4-CD28-CD3z T 细胞增强针对 CD80/CD86 阳性 B 细胞恶性肿瘤的抗肿瘤活性
DOI：
10.3389/fimmu.2021.642528
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发表时间：
2021
影响因子：
7.3
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Lin S;Cheng L;Ye W;Li S;Zheng D;Qin L;Wu Q;Long Y;Lin S;Wang S;Huang G;Li P;Yao Y;Sun X
The adoptive transfer of chimeric antigen receptor T (CAR T) cells have been recognized as a promising therapeutic strategy for the treatment of hematological malignancies; however, clinical success using CAR T cells for the treatment of solid tumors are still limited since the T-cell function is inhibited by negative signals in the microenvironment of solid tumors. CTLA4 is a well-known immune checkpoint molecule, thus we developed a novel CAR by converting this negative signal to positive signal. The CAR developed consists of the extracellular and transmembrane domains of CTLA4 and the cytoplasmic domains of CD28 and CD3z (CTLA4-CAR T). CTLA4-CAR T cells exhibited superior cytokine secreting activities and cytotoxic to tumor cells in vitro and in xenograft models. CTLA4-CAR T cells were found to accumulate in tumors and are toxic to myeloid-derived suppressor cells (MDSCs) without signs of severe GVHD and CRS in preclinical models. Thus, this chimeric CTLA4-CAR can enhance the antitumor activity of CAR T cells and shed light on the strategy of using armed CAR T cells to target the immunomodulatory tumor microenvironment.
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影响因子：
82.9
作者：
Giavridis T;van der Stegen SJC;Eyquem J;Hamieh M;Piersigilli A;Sadelain M
通讯作者：
Sadelain M
影响因子：
82.9
作者：
Long, Adrienne H.;Haso, Waleed M.;Shern, Jack F.;Wanhainen, Kelsey M.;Murgai, Meera;Ingaramo, Maria;Smith, Jillian P.;Walker, Alec J.;Kohler, M. Eric;Venkateshwara, Vikas R.;Kaplan, Rosandra N.;Patterson, George H.;Fry, Terry J.;Orentas, Rimas J.;Mackall, Crystal L.
通讯作者：
Mackall, Crystal L.
嵌合抗原受体修饰 T 细胞治疗 HER2 阳性晚期胆道癌和胰腺癌的 I 期研究。
影响因子：
21.1
作者：
Feng K;Liu Y;Guo Y;Qiu J;Wu Z;Dai H;Yang Q;Wang Y;Han W
通讯作者：
Han W
影响因子：
76.2
作者：
Calabro, Luana;Morra, Aldo;Maio, Michele
通讯作者：
Maio, Michele
DOI：
10.1038/nrc.2016.97
发表时间：
2016-08-23
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Fesnak AD;June CH;Levine BL
通讯作者：
Levine BL