PDF(Pubmed)
Abstract：
UNASSIGNED: Chimeric antigen receptor T (CAR-T) cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies. However, there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T (CAR-T) cell therapy, as well as the optimal timing for CAR-T cell infusion post-chemotherapy.
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.
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.
摘要：
■嵌合抗原受体T(CAR-T)细胞疗法在改善血液恶性肿瘤方面取得了显著的治疗成功。然而,在嵌合抗原受体T（CAR-T）细胞疗法之前，临床指南中关于最有效的化疗方案存在空白，以及化疗后CAR-T细胞输注的最佳时机。
■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.
■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.
