Clara Helena Klee, Alicia Villatoro, Nicholas Paul Casey, Else Marit Inderberg, Sébastien Wälchli
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引用次数: 0
摘要
嵌合抗原受体（CAR）T 细胞（CAR T）已成为癌症患者的一种潜在疗法。CAR T 细胞能够识别癌细胞上的膜蛋白，从而启动 T 细胞的下游信号传导，最终导致癌细胞死亡。长期持续接触抗原、激活抑制信号通路和/或慢性炎症会导致 CAR T 细胞衰竭。在这种情况下，CAR 的设计会对 CAR T 细胞的功能、效力和衰竭产生重大影响。在这里，我们以 CD19CAR 为模型，提供了一种再挑战方案，即每周用恶性淋巴细胞系 BL-41 和 Nalm-6 培养 CAR T 细胞，以模拟它们在四周内持续承受抗原压力的情况。该方案可用于评估 CAR T 细胞的功能和比较不同的 CAR 构建物。
Chimeric antigen receptor (CAR) T cells (CAR T) have emerged as a potential therapy for cancer patients. CAR T cells are capable of recognizing membrane proteins on cancer cells which initiates a downstream signaling in T cells that ends in cancer cell death. Continuous antigen exposure over time, activation of inhibitory signaling pathways and/or chronic inflammation can lead to CAR T cell exhaustion. In this context, the design of CARs can have a great impact on the functionality of CAR T cells, on their potency and exhaustion. Here, using CD19CAR as model, we provide a re-challenge protocol where CAR T cells are cultured weekly with malignant lymphoid cell lines BL-41 and Nalm-6 to simulate them with continuous antigen pressure over a four-week period. This protocol can be value for assessing CAR T cell functionality and for the comparison of different CAR constructs.
期刊介绍：
For over fifty years, Methods in Cell Biology has helped researchers answer the question "What method should I use to study this cell biology problem?" Edited by leaders in the field, each thematic volume provides proven, state-of-art techniques, along with relevant historical background and theory, to aid researchers in efficient design and effective implementation of experimental methodologies. Over its many years of publication, Methods in Cell Biology has built up a deep library of biological methods to study model developmental organisms, organelles and cell systems, as well as comprehensive coverage of microscopy and other analytical approaches.
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