在嵌合抗原受体细胞疗法中，目标异构体是一个被忽视的挑战与机遇。

Bogetofte Barnkob Mike, Vitting-Seerup Kristoffer, Rønn Olsen Lars

Centre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Department of Clinical Immunology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.

Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.

Immunother Adv. 2022 Apr 20;2(1):ltac009. doi: 10.1093/immadv/ltac009. eCollection 2022.

The development of novel chimeric antigen receptor (CAR) cell therapies is rapidly growing, with 299 new agents being reported and 109 new clinical trials initiated so far this year. One critical lesson from approved CD19-specific CAR therapies is that target isoform switching has been shown to cause tumour relapse, but little is known about the isoforms of CAR targets in solid cancers. Here we assess the protein isoform landscape and identify both the challenges and opportunities protein isoform switching present as CAR therapy is applied to solid cancers.

新型嵌合抗原受体（CAR）细胞疗法正在迅速发展，今年到目前为止已有299种新药物被报道，109项新临床试验启动。已获批的CD19特异性CAR疗法带来的一个关键教训是，靶点异构体转换已被证明会导致肿瘤复发，但对于实体癌中CAR靶点的异构体却知之甚少。在此，我们评估了蛋白质异构体情况，并确定了在将CAR疗法应用于实体癌时蛋白质异构体转换带来的挑战和机遇。