From the Division of Clinical Science, Department of Blood & Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center.
Cancer J. 2021;27(2):92-97. doi: 10.1097/PPO.0000000000000514.
The US Food and Drug Administration has approved 3 chimeric antigen receptor (CAR) T-cell therapies. For continued breakthroughs, novel CAR designs are needed. This includes different antigen-binding domains such as antigen-ligand binding partners and variable lymphocyte receptors. Another recent advancement in CAR design is Boolean logic gates that can minimize on-target, off-tumor toxicities. Recent studies on the optimization of costimulatory signaling have also shown how CAR design can impact function. By using specific signaling pathways and transcription factors, CARs can impact T-cell gene expression to enhance function. By using these techniques, the promise of CAR T-cell therapies for solid tumors can be fulfilled.
美国食品和药物管理局已经批准了 3 种嵌合抗原受体（CAR）T 细胞疗法。为了持续取得突破，需要新型的 CAR 设计。这包括不同的抗原结合结构域，如抗原-配体结合伴侣和可变淋巴细胞受体。CAR 设计的另一个最新进展是布尔逻辑门，可以最大限度地减少靶标、肿瘤外毒性。最近关于共刺激信号优化的研究也表明了 CAR 设计如何影响功能。通过使用特定的信号通路和转录因子，CAR 可以影响 T 细胞基因表达，从而增强功能。通过使用这些技术，可以实现 CAR T 细胞疗法治疗实体瘤的承诺。
