1 Institute of Experimental Hematology, Hannover Medical School , Hannover, Germany .
2 REBIRTH Cluster of Excellence, Hannover Medical School , Hannover, Germany .
Hum Gene Ther. 2018 Oct;29(10):1083-1097. doi: 10.1089/hum.2017.251. Epub 2018 Aug 29.
Successful translation of chimeric antigen receptor (CAR) T cells designed to target and eradicate CD19+ lymphomas has emboldened scientists and physicians worldwide to explore the possibility of applying CAR T-cell technology to other tumor entities, including solid tumors. Next-generation strategies such as fourth-generation CARs (CAR T cells redirected for universal cytokine killing, also known as TRUCKs) designed to deliver immunomodulatory cytokines to the tumor microenvironment, dual CAR designs to improve tumor control, inclusion of suicide genes as safety switches, and precision genome editing are currently being investigated. One major ongoing goal is to determine how best to generate CAR T cells that modulate the tumor microenvironment, overcome tumor survival mechanisms, and thus allow broader applicability as universal allogeneic T-cell therapeutics. Development of state-of-the-art and beyond viral vector systems to deliver designer CARs coupled with targeted genome editing is expected to generate more effective off-the-shelf CAR T cells with activity against a greater number of cancer types and importantly solid tumors.
嵌合抗原受体 (CAR) T 细胞的成功转化设计用于靶向和消除 CD19+淋巴瘤，这一成就鼓舞了世界各地的科学家和医生探索将 CAR T 细胞技术应用于其他肿瘤实体的可能性，包括实体瘤。下一代策略，如第四代 CAR（CAR T 细胞重新定向用于通用细胞因子杀伤，也称为 TRUCKs）旨在将免疫调节细胞因子递送至肿瘤微环境、双 CAR 设计以改善肿瘤控制、包含自杀基因作为安全开关，以及精确基因组编辑，目前正在研究中。一个主要的持续目标是确定如何最好地生成调节肿瘤微环境、克服肿瘤生存机制的 CAR T 细胞，从而使作为通用同种异体 T 细胞治疗剂的更广泛适用性成为可能。先进的和超越病毒载体系统的开发用于传递设计 CAR 与靶向基因组编辑有望产生更有效的现成 CAR T 细胞，这些细胞对更多种类的癌症具有活性，重要的是对实体瘤具有活性。
