芪银三两三汤增强抗 CD19 CAR-T 细胞在 B 细胞淋巴瘤治疗中的功能

Network pharmacology analyses, in vitro and in vivo studies, and transcriptome sequencing analyses were performed.

Forty-two components were detected in SLS by HPLC. Sixteen pharmacologically active ingredients were analyzed by searching the TCMSP database. The predicted targets included IL-2, IL-6, IL-10, TNF- , CASP7, and CASP9. In vitro studies revealed that SLS can dose-dependently promote the killing effect of unmodified T and anti-CD19 CAR-T cells against Raji cell lines. Meanwhile, SLS inhibited unmodified T and anti-CD19 CAR-T cell exhaustion, promoted anti-CD19 CAR-T cell proliferation, reduced the levels of IL-6, IL-10, and TNF- , and increased granzyme B levels. In vivo studies, SLS effectively improved the anti-tumor function of anti-CD19 CAR-T cells, prolonged the survival of the mice, and reduced the levels of IL-6, GM-CSF, and IL-17. Subsequently, the transcriptomic analysis showed that SLS inhibited the IL-17 signaling pathway and the apoptosis signaling pathway of T cells. In addition, SLS downregulated the expression of IL-17A, IL-6, TNF- , GM-CSF, S100A8, CASP 7, CASP 9, and CASP 10 in anti-CD19 CAR-T cells. SLS regulated the IL-17 signaling pathway and apoptosis signaling pathway in anti-CD19 CAR-T cells.

SLS plays a potential auxiliary role in enhancing the function of anti-CD19 CAR T cells in the treatment of B-cell lymphoma, improving the killing ability of these cells, reducing the potential risk associated with inflammation, and providing synergistic and attenuating effects. The mechanism of SLS is partially mediated by the apoptosis and IL-17 signaling pathways (such as IL-17A, IL-6, TNF- , GM-CSF, and Granzyme B).