Optimization of lymphapheresis for manufacturing autologous CAR-T cells
Optimization of lymphapheresis for manufacturing autologous CAR-T cells
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DOI：
10.1007/s12185-021-03191-x
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发表时间：
2021-07-17
影响因子：
2.1
通讯作者：
Kunisaki, Yuya
中科院分区：
文献类型：
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作者：
Yamanaka, Ikumi;Yamauchi, Takuji;Kunisaki, Yuya
通过淋巴细胞分离术收集CD 3+淋巴细胞对于制备自体嵌合抗原受体（CAR）T细胞至关重要。优化每个患者的淋巴细胞分离术的时间和程序至关重要，因为患者通常患有进行性疾病并接受可能减少T细胞计数的药物。我们对28例接受淋巴细胞分离术用于使用tisagenlecleucel进行CD 19定向CAR-T治疗的患者的临床数据进行了回顾性研究，以确定可能影响CD 3+淋巴细胞产量的因素。外周血中的CD 3+细胞数量与CD 3+细胞产量显著相关（相关系数r = 0.84），这使我们能够估计单采前要处理的血液体积。我们还发现，单采部位的小细胞比率（SCR）准确地反映了淋巴细胞的比例，尤其是在没有循环原始细胞的患者中（决定系数：r（2）= 0.9）。我们能够通过测量单采前循环CD 3+细胞计数和监测SCR来预测CD 3+细胞产量并防止过度单采。总的来说，这些结果将帮助我们建立一种策略，用于在逐个患者的基础上优化CAR-T细胞生产的淋巴细胞分离程序。
Collection of CD3+ lymphocytes via lymphapheresis is essential for manufacturing autologous chimeric antigen receptor (CAR) T cells. Optimization of timing and procedures for lymphapheresis for each patient is critical because patients often have progressive diseases and receive medications that could reduce T cell counts. We conducted a retrospective study of clinical data from 28 patients who underwent lymphapheresis for CD19-directed CAR-T therapy with tisagenlecleucel to identify factors that could affect CD3+ lymphocyte yields. The numbers of CD3+ cells in peripheral blood were significantly correlated with CD3+ cell yields (correlation coefficient r = 0.84), which enabled us to estimate the volume of blood to process before apheresis. We also found that small cell ratio (SCR) at the apheresis site precisely reflected the proportion of lymphocytes, especially in patients without circulating blasts (coefficient of determination: r(2) = 0.9). We were able to predict the CD3+ cell yield and prevent excessive apheresis by measuring pre-apheresis circulating CD3+ cell counts and monitoring SCR. Collectively, these results will help us to establish a strategy for optimization of lymphapheresis procedures for CAR-T cell production on a patient-by-patient basis.