Won-Ho Lee, Charlotte E. Graham, Hadley R. Wiggin, Hannah K. Nolan, Kiana J. Graham, Felix Korell, Mark B. Leick, Alexis L. Barselau, Estelle Emmanuel-Alejandro, Michael A. Trailor, Juliane M. Gildea, Frederic Preffer, Matthew J. Frigault, Marcela V. Maus, Kathleen M. E. Gallagher
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引用次数: 0
摘要
以 BCMA 为靶点的嵌合抗原受体(CAR)修饰 T 细胞疗法在治疗多发性骨髓瘤方面显示出令人瞩目的活性。目前有两种获得 FDA 许可的产品:ciltacabtagene autoleucel 和 idecabtagene vicleucel,用于治疗复发和难治性疾病。虽然产品制造商在临床试验中进行了相关分析,但对于希望将其作为临床结果生物标志物的医生和研究人员来说,可靠的 BCMA CAR T 检测分析方法选择有限。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、准确地量化患者血液中的 BCMA CAR T 细胞是一项宝贵的资产。在此,我们优化了一种准确灵敏的流式细胞术检测方法,该方法使用 PE 结合物可溶性 BCMA 蛋白,定量下限为 CD3+ T 细胞的 0.19%,适合作为常规检测方法,用于监测接受 ciltacabtagene autoleucel 或 idecabtagene vicleucel 治疗的患者血液中 BCMA CAR T 细胞的频率。
Optimization of a flow cytometry test for routine monitoring of B cell maturation antigen targeted CAR in peripheral blood
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.