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优化流式细胞术检测外周血中 B 细胞成熟抗原靶向嵌合抗原受体的方法,以进行常规监测。

Optimization of a flow cytometry test for routine monitoring of B cell maturation antigen targeted CAR in peripheral blood.

机构信息

Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

Department of Pathology and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Cytometry B Clin Cytom. 2024 May;106(3):162-170. doi: 10.1002/cyto.b.22165. Epub 2024 Feb 28.

Abstract

Chimeric antigen receptor (CAR) modified T cell therapies targeting BCMA have displayed impressive activity in the treatment of multiple myeloma. There are currently two FDA licensed products, ciltacabtagene autoleucel and idecabtagene vicleucel, for treating relapsed and refractory disease. Although correlative analyses performed by product manufacturers have been reported in clinical trials, there are limited options for reliable BCMA CAR T detection assays for physicians and researchers looking to explore it as a biomarker for clinical outcome. Given the known association of CAR T cell expansion kinetics with toxicity and response, being able to quantify BCMA CAR T cells routinely and accurately in the blood of patients can serve as a valuable asset. Here, we optimized an accurate and sensitive flow cytometry test using a PE-conjugated soluble BCMA protein, with a lower limit of quantitation of 0.19% of CD3+ T cells, suitable for use as a routine assay for monitoring the frequency of BCMA CAR T cells in the blood of patients receiving either ciltacabtagene autoleucel or idecabtagene vicleucel.

摘要

嵌合抗原受体(CAR)修饰的 T 细胞疗法靶向 BCMA 在多发性骨髓瘤的治疗中显示出了令人印象深刻的疗效。目前有两种获得 FDA 批准的产品,cilta-cabtagene autoleucel 和 idecabtagene vicleucel,用于治疗复发和难治性疾病。尽管产品制造商在临床试验中已经进行了相关的分析,但对于希望将其作为临床结果生物标志物进行探索的医生和研究人员来说,可靠的 BCMA CAR T 检测检测方法选择有限。鉴于 CAR T 细胞扩增动力学与毒性和反应的已知关联,能够常规且准确地定量患者血液中的 BCMA CAR T 细胞,可以成为一项有价值的资产。在这里,我们使用 PE 缀合的可溶性 BCMA 蛋白优化了一种准确且灵敏的流式细胞术检测方法,其检测下限为 CD3+T 细胞的 0.19%,可用于常规检测接受 cilta-cabtagene autoleucel 或 idecabtagene vicleucel 治疗的患者血液中 BCMA CAR T 细胞的频率。

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