Genetic engineering of T cells with chimeric antigen receptors for hematological malignancy immunotherapy
Genetic engineering of T cells with chimeric antigen receptors for hematological malignancy immunotherapy
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具有嵌合抗原受体的 T 细胞基因工程用于血液恶性肿瘤免疫治疗
DOI：
10.1007/s11427-018-9411-4
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
韩为东
中科院分区：
文献类型：
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作者：
遆冬冬;伍志强;付小兵;韩为东
宿主免疫系统通过识别和摧毁癌细胞，在监测和消除肿瘤方面发挥着重要作用。近几十年来，研究主要集中在利用工程T细胞进行过继免疫治疗以治疗恶性疾病。通过将患者自身的T细胞与嵌合抗原受体(CAR)基因植入，它们可以有效识别肿瘤特异性抗原，并以不依赖MHC的方式选择性地清除靶细胞。到目前为止，CAR-T细胞疗法已经在B细胞白血病患者中显示出巨大的临床疗效。由于不同的CAR设计和肿瘤复杂的微环境，基因重定向的T细胞可能产生不同的生物学特性，从而影响其长期临床表现和预后。同时，CAR-T细胞应用引起的一些意想不到的毒性也被检测出来，并限制了疗效。多种重要参数与过继转移的细胞行为密切相关，包括CAR-T细胞归巢、CAR构成信号、T细胞分化和耗竭。因此，了解CARS分子设计以提高输注细胞的有效性和安全性对正在考虑这种新的癌症疗法的临床医生和患者至关重要。本文就CAR-T细胞治疗的研究进展、临床应用的局限性和前景作一综述。
The host immune system plays an instrumental role in the surveillance and elimination of tumors by recognizing and destroying cancer cells. In recent decades, studies have mainly focused on adoptive immunotherapy using engineered T cells for the treatment of malignant diseases. Through gene engraftment of the patient’s own T cells with chimeric antigen receptor (CAR), they can recognize tumor specific antigens effectively and eradicate selectively targeted cells in an MHC-independent fashion. To date, CAR-T cell therapy has shown great clinical utility in patients with B-cell leukemias. Owing to different CAR designs and tumor complex microenvironments, genetically redirected T cells may generate diverse biological properties and thereby impact their long-term clinical performance and outcome. Meanwhile some unexpected toxicities that result from CAR-T cell application have been examined and limited the curative effects. Diverse important parameters are closely related with adoptively transferred cell behaviors, including CAR-T cells homing, CAR constitutive signaling, T cell differentiation and exhaustion. Thus, understanding CARs molecular design to improve infused cell efficacy and safety is crucial to clinicians and patients who are considering this novel cancer therapeutics. In this review, the developments in CAR-T cell therapy and the limitations and perspectives in optimizing this technology towards clinical application are discussed.
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影响因子：
10.1
作者：
Hudecek M;Sommermeyer D;Kosasih PL;Silva-Benedict A;Liu L;Rader C;Jensen MC;Riddell SR
通讯作者：
Riddell SR
影响因子：
16.6
作者：
Klein-Hessling S;Muhammad K;Klein M;Pusch T;Rudolf R;Flöter J;Qureischi M;Beilhack A;Vaeth M;Kummerow C;Backes C;Schoppmeyer R;Hahn U;Hoth M;Bopp T;Berberich-Siebelt F;Patra A;Avots A;Müller N;Schulze A;Serfling E
通讯作者：
Serfling E
影响因子：
12.8
作者：
Cartellieri M;Feldmann A;Koristka S;Arndt C;Loff S;Ehninger A;von Bonin M;Bejestani EP;Ehninger G;Bachmann MP
通讯作者：
Bachmann MP
CAR-T细胞疗法新进展
影响因子：
28.5
作者：
Wang Z;Wu Z;Liu Y;Han W
通讯作者：
Han W
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
Yajing Zhang;Wen-ying Zhang;Hanren Dai;Yao Wang;F. Shi;Chunmeng Wang;Ye-lei Guo;Yang Liu;
通讯作者：
Yajing Zhang;Wen-ying Zhang;Hanren Dai;Yao Wang;F. Shi;Chunmeng Wang;Ye-lei Guo;Yang Liu;