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A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism
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A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism
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Journal Article
A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism
2024
Overview
Memory T cells demonstrate superior in vivo persistence and antitumor efficacy. However, methods for manufacturing less differentiated T cells are not yet well-established. Here, we show that producing chimeric antigen receptor (CAR)-T cells using berbamine (BBM), a natural compound found in the Chinese herbal medicine Berberis amurensis, enhances the antitumor efficacy of CAR-T cells. BBM is identified through cell-based screening of chemical compounds using induced pluripotent stem cell-derived T cells, leading to improved viability with a memory T cell phenotype. Transcriptomics and metabolomics using stem cell memory T cells reveal that BBM broadly enhances lipid metabolism. Furthermore, the addition of BBM downregulates the phosphorylation of p38 mitogen-activated protein kinase and enhanced mitochondrial respiration. CD19-CAR-T cells cultured with BBM also extend the survival of leukaemia mouse models due to their superior in vivo persistence. This technology offers a straightforward approach to enhancing the antitumor efficacy of CAR-T cells.
When used in CAR-T cell processing, the plant alkaloid berbamine prolongs the survival of leukemic animals by boosting CAR-T cell viability, memory phenotype, and persistence by modulating cellular metabolism, including mitochondrial respiration.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 13/106
/ 38/91
/ 42/109
/ 64
/ 64/60
/ Animals
/ Benzylisoquinolines - pharmacology
/ Biomedical and Life Sciences
/ Cell Culture Techniques - methods
/ Humans
/ Immunotherapy, Adoptive - methods
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - drug effects
/ Induced Pluripotent Stem Cells - metabolism
/ Kinases
/ Leukemia
/ Mice
/ Receptors, Chimeric Antigen - genetics
/ Receptors, Chimeric Antigen - immunology
/ Receptors, Chimeric Antigen - metabolism
