Deciphering the importance of culture pH on CD22 CAR T-cells characteristics.

Autor:	Prochazkova M; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Dreyzin A; Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC, USA., Shao L; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Garces P; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Cai Y; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Shi R; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Pelayo A; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Kim YS; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Pham V; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Frodigh SE; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Fenton S; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Karangwa C; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Su Y; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Martin K; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Zhang N; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Highfill SL; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Somerville RP; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Shah NN; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Stroncek DF; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Jin P; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA. pjin@mail.cc.nih.gov.
Jazyk:	angličtina
Zdroj:	Journal of translational medicine [J Transl Med] 2024 Apr 24; Vol. 22 (1), pp. 384. Date of Electronic Publication: 2024 Apr 24.
DOI:	10.1186/s12967-024-05197-5
Abstrakt:	Background: Chimeric antigen receptor (CAR) T-cells have demonstrated significant efficacy in targeting hematological malignancies, and their use continues to expand. Despite substantial efforts spent on the optimization of protocols for CAR T-cell manufacturing, critical parameters of cell culture such as pH or oxygenation are rarely actively monitored during cGMP CAR T-cell generation. A comprehensive understanding of the role that these factors play in manufacturing may help in optimizing patient-specific CAR T-cell therapy with maximum benefits and minimal toxicity. Methods: This retrospective study examined cell culture supernatants from the manufacture of CAR T-cells for 20 patients with B-cell malignancies enrolled in a phase 1/2 clinical trial of anti-CD22 CAR T-cells. MetaFLEX was used to measure supernatant pH, oxygenation, and metabolites, and a Bio-Plex assay was used to assess protein levels. Correlations were assessed between the pH of cell culture media throughout manufacturing and cell proliferation as well as clinical outcomes. Next-generation sequencing was conducted to examine gene expression profiles of the final CAR T-cell products. Results: A pH level at the lower range of normal at the beginning of the manufacturing process significantly correlated with measures of T-cell expansion and metabolism. Stable or rising pH during the manufacturing process was associated with clinical response, whereas a drop in pH was associated with non-response. Conclusions: pH has potential to serve as an informative factor in predicting CAR T-cell quality and clinical outcomes. Thus, its active monitoring during manufacturing may ensure a more effective CAR T-cell product. (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze:	MEDLINE
Externí odkaz:	Full text from SpringerLink