Effects of Rapamycin on the Function of CAR-T cells
MAO Juan1,2, ZHANG Yueqin3, LIU Qin3, LIU Yang3, LI Hua2 *
To investigate the effects of rapamycin on the specific killing of CAR-T (chimeric antigen receptor T) cells, the expansion and cytokine secretion of CAR-T cells in vitro. This study used a T cell specific killing model in which the effect cells were the CAR-T targeting CD19 and the target cells were CD19+ CD22+ Raji cells. Under different effect-target ratio with various rapamycin concentration at various drug administration time, the specific killing rates of CAR-T were detected by flow cytometry absolute count and it was found that rapamycin did not affect the killing ability of CAR-T cells. Using CFSE (carboxyfluorescein diacetate succinimidyl ester) to detect the expansion ability of CAR-T cells, it was found that rapamycin could slow down the increase rate of CAR-T cells number by inhibiting their proliferation rather than promoting apoptosis. Using flow cytometry CBA (cytometric bead array) to detect cytokine secretion, it was found that rapamycin could significantly inhibited cytokines secretion level of CAR-T cells after activation by target cells. In summary, rapamycin can reduce the secretion level of inflammatory cytokines without affecting the killing function of CAR-T cells.
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