Chimeric antigen receptor (CAR)-T cells are emerging as a generation-defining therapeutic however their manufacture remains a major barrier to meeting increased market demand. Monitoring critical quality attributes (CQAs) and critical process parameters (CPPs) during manufacture would vastly enrich acquired information related to the process and product, providing feedback to enable real-time decision making. Here we identify specific CAR-T cytokines as value-adding analytes and discuss their roles as plausible CPPs and CQAs. High sensitivity sensing technologies which can be easily integrated into manufacture workflows are essential to implement real-time monitoring of these cytokines. We therefore present biosensors as enabling technologies and evaluate recent advancements in cytokine detection in cell cultures, offering promising translatability to CAR-T biomanufacture. Finally, we outline emerging sensing technologies with future promise, and provide an overall outlook on existing gaps to implementation and the optimal sensing platform to enable cytokine monitoring in CAR-T biomanufacture.

中文翻译：

---

测量细胞因子的综合视角为 CAR-T 生物加工提供信息


嵌合抗原受体 (CAR)-T 细胞正在成为一代定义疗法，但其制造仍然是满足不断增长的市场需求的主要障碍。在制造过程中监控关键质量属性 (CQA) 和关键工艺参数 (CPP) 将极大地丰富所获取的与工艺和产品相关的信息，提供反馈以实现实时决策。在这里，我们将特定的 CAR-T 细胞因子确定为增值分析物，并讨论它们作为合理的 CPP 和 CQA 的作用。可以轻松集成到制造工作流程中的高灵敏度传感技术对于实现这些细胞因子的实时监测至关重要。因此，我们将生物传感器作为使能技术，并评估细胞培养物中细胞因子检测的最新进展，为 CAR-T 生物制造提供有前途的可转化性。最后，我们概述了具有未来前景的新兴传感技术，并对现有的实施差距和最佳传感平台进行了总体展望，以实现 CAR-T 生物制造中细胞因子的监测。