UNASSIGNED: We employed cell-derived tumor xenograft (CDX) murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment. Furthermore, transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.
UNASSIGNED: Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine, followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy, exerts the most efficacious therapeutic effect in B-cell hematological malignancies. Concurrently, RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism, primarily through the inhibition of key mitochondrial targets, such as C-Jun Kinase enzyme (C-JUN).
UNASSIGNED: In summary, the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.
■我们采用细胞来源的肿瘤异种移植(CDX)鼠模型来描绘最佳预处理化疗方案和CAR-T细胞治疗的时机。此外,实施转录组测序以鉴定治疗靶标并阐明控制治疗方案的潜在机制。
■我们的临床前体内评估确定环磷酰胺和氟达拉滨的组合,随后在化疗后五天输注CD19CAR-T细胞,在B细胞血液系统恶性肿瘤中发挥最有效的治疗作用。同时,RNA-seq数据表明,治疗功效主要扰乱肿瘤细胞代谢,主要通过抑制关键的线粒体靶标,例如C-Jun激酶酶(C-JUN)。
■总之,本研究为CD19CAR-T细胞疗法在B细胞恶性血液病治疗中的应用提供了重要的临床指导,并成为权威参考.