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A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism

GSE264206 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/05/02 Platform GPL24676
Summary
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.
Published in
A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism
Takayanagi SI, Chuganji S, Tanaka M et al. · Communications biology 2024 · PMID 38834758 · doi:10.1038/s42003-024-06297-0
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Also filed as BioProject PRJNA1101460 and SRA study SRP502362. Searching any of these in the dataset finder brings you back here.

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