自体 CAR-T 细胞生产中的淋巴细胞单采优化

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.