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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

ZHIGANG XIA1,#, MENGYAO TIAN1,#, YUCAI CHENG1, WENFANG YI1, ZEFAN DU1,2, TIANWEN LI1,2, YUCHEN WEN1, LINDI LI1,2, YONG LIU1,2,*, CHUN CHEN1,*

1 Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China
2 Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China

* Corresponding Authors: YONG LIU. Email: email; CHUN CHEN. Email: email

Oncology Research 2024, 32(6), 1109-1118. https://doi.org/10.32604/or.2024.049792

Abstract

Background: 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. Materials and Methods: 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. Results: 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). Conclusion: 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.

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APA Style
XIA, Z., TIAN, M., CHENG, Y., YI, W., DU, Z. et al. (2024). Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of b-cell hematologic malignancies in vivo. Oncology Research, 32(6), 1109-1118. https://doi.org/10.32604/or.2024.049792
Vancouver Style
XIA Z, TIAN M, CHENG Y, YI W, DU Z, LI T, et al. Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of b-cell hematologic malignancies in vivo. Oncol Res. 2024;32(6):1109-1118 https://doi.org/10.32604/or.2024.049792
IEEE Style
Z. XIA et al., "Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo," Oncol. Res., vol. 32, no. 6, pp. 1109-1118. 2024. https://doi.org/10.32604/or.2024.049792



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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