Children's Hospital, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Experimental Immunology, Goethe University Frankfurt, Frankfurt am Main, Germany.
Gene Ther. 2021 Sep;28(9):513-527. doi: 10.1038/s41434-021-00246-w. Epub 2021 Mar 22.
Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. Lately, CAR-NK cell therapies have also come into focus as novel therapeutic options to address hurdles related to CAR-T cell therapies, such as therapy-induced side effects. Currently, more than 500 CAR-T and 17 CAR-NK cell trials are being conducted worldwide including the four CAR-T cell products Kymriah, Yescarta, Tecartus and Breyanzi, which are already available on the market. Most CAR-T cell-based gene therapy products that are under clinical evaluation consist of autologous enriched T cells, whereas CAR-NK cell-based approaches can be generated from allogeneic donors. Besides modification based on a second-generation CAR, more advanced CAR-immune cell therapeutics are being tested, which utilize precise insertion of genes to circumvent graft-versus-host disease (GvHD) or employ a dual targeting approach and adapter CARs in order to avoid therapy resistance caused by antigen loss. In this review, we are going to take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany.
嵌合抗原受体 (CAR)-T 细胞疗法即将成为治疗血液系统疾病的强大免疫治疗工具,以应对迫切的医疗需求。最近,CAR-NK 细胞疗法也成为解决 CAR-T 细胞疗法相关障碍的新治疗选择,例如治疗相关的副作用。目前,全球正在进行超过 500 项 CAR-T 和 17 项 CAR-NK 细胞试验,包括已经上市的四种 CAR-T 细胞产品 Kymriah、Yescarta、 Tecartus 和 Breyanzi。大多数正在临床评估的基于 CAR-T 细胞的基因治疗产品由自体富集的 T 细胞组成,而基于 CAR-NK 细胞的方法可以由同种异体供体产生。除了基于第二代 CAR 的修饰外,还正在测试更先进的 CAR-免疫细胞疗法,这些疗法利用基因的精确插入来规避移植物抗宿主病 (GvHD),或采用双重靶向方法和适配器 CAR,以避免因抗原丢失引起的治疗耐药性。在这篇综述中,我们将更详细地了解商业 CAR-T 细胞疗法,以及正在德国进行临床试验评估的 CAR-T 和 CAR-NK 细胞产品。
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