Chimeric antigen receptor T-cell therapy in glioblastoma: charging the T cells to fight.
Chimeric antigen receptor T-cell therapy in glioblastoma: charging the T cells to fight.
复制标题
DOI：
10.1186/s12967-020-02598-0
复制
发表时间：
2020-11-11
影响因子：
7.4
通讯作者：
Xie Q
中科院分区：
文献类型：
--
作者：
Land CA;Musich PR;Haydar D;Krenciute G;Xie Q
多形性胶质母细胞瘤（GBM）是最常见的恶性脑癌，它侵入正常脑组织并阻碍手术根除，导致早期局部复发和高死亡率。此外，大多数治疗剂缺乏穿过血脑屏障（BBB）的渗透性，进一步降低了化疗的功效。因此，针对GBM的有效治疗需要肿瘤特异性靶点和有效的颅内药物递送。随着免疫疗法的最新进展，具有嵌合抗原受体（汽车）的基因工程T细胞正在成为治疗癌症的有希望的方法。通过用含有与信号传导T细胞受体的恒定区连接的肿瘤相关抗原（TAA）识别结构域的CAR构建体转导T淋巴细胞，CAR T细胞可以以非MHC限制性方式以高特异性识别预定义的TAA，并且不依赖于抗原加工。活性T细胞可以穿过BBB，为药物递送和肿瘤靶向提供额外的优势。在这里，我们回顾了CAR设计和技术创新，临床前和临床开发中的主要目标，重点是GBM，以及为提高CAR T细胞功效而开发的多种策略。
Glioblastoma multiforme (GBM) is the most common malignant brain cancer that invades normal brain tissue and impedes surgical eradication, resulting in early local recurrence and high mortality. In addition, most therapeutic agents lack permeability across the blood brain barrier (BBB), further reducing the efficacy of chemotherapy. Thus, effective treatment against GBM requires tumor specific targets and efficient intracranial drug delivery. With the most recent advances in immunotherapy, genetically engineered T cells with chimeric antigen receptors (CARs) are becoming a promising approach for treating cancer. By transducing T lymphocytes with CAR constructs containing a tumor-associated antigen (TAA) recognition domain linked to the constant regions of a signaling T cell receptor, CAR T cells may recognize a predefined TAA with high specificity in a non-MHC restricted manner, and is independent of antigen processing. Active T cells can travel across the BBB, providing additional advantage for drug delivery and tumor targeting. Here we review the CAR design and technical innovations, the major targets that are in pre-clinical and clinical development with a focus on GBM, and multiple strategies developed to improve CAR T cell efficacy.
登录
查看更多内容
影响因子：
--
作者：
Filley AC;Henriquez M;Dey M
通讯作者：
Dey M
影响因子：
6.4
作者：
Golinelli, Giulia;Grisendi, Giulia;Dominici, Massimo
通讯作者：
Dominici, Massimo
影响因子：
4.2
作者：
Dardevet L;Rani D;Aziz TA;Bazin I;Sabatier JM;Fadl M;Brambilla E;De Waard M
通讯作者：
De Waard M
影响因子：
45.3
作者：
Ahmed, Nabil;Brawley, Vita S.;Gottschalk, Stephen
通讯作者：
Gottschalk, Stephen
DOI：
10.1158/1078-0432.ccr-09-1322
发表时间：
2010-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Ahmed N;Salsman VS;Kew Y;Shaffer D;Powell S;Zhang YJ;Grossman RG;Heslop HE;Gottschalk S
通讯作者：
Gottschalk S