2. Academic Validation
  3. A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism

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

  • Commun Biol. 2024 Jun 4;7(1):685. doi: 10.1038/s42003-024-06297-0.
Shin-Ichiro Takayanagi # 1 2 3,  Sayaka Chuganji # 4 5,  Masahiro Tanaka 5,  Bo Wang 5,  Saki Hasegawa 4 5,  Ken Fukumoto 4 5,  Nariaki Wasano 4,  Makoto Kakitani 4,  Nakaba Ochiai 4 5,  Yohei Kawai 5,  Tatsuki Ueda 5,  Akihiro Ishikawa 5,  Yuko Kurimoto 4,  Asami Fukui 4,  Sanae Kamibayashi 5,  Eri Imai 5,  Atsushi Kunisato 4,  Hajime Nozawa 4,  Shin Kaneko 6
Affiliations

Affiliations

  • 1 Kirin Central Research Institute, Kirin Holdings Company, Ltd., 26-1, Muraoka-Higashi 2, Fujisawa, Kanagawa, 251-8555, Japan. shinichiro.takayanagi.ky@kyowakirin.com.
  • 2 Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. shinichiro.takayanagi.ky@kyowakirin.com.
  • 3 Biomedical Science Research Laboratories 2, Research Division, Kyowa Kirin Co., Ltd., Tokyo, Japan. shinichiro.takayanagi.ky@kyowakirin.com.
  • 4 Kirin Central Research Institute, Kirin Holdings Company, Ltd., 26-1, Muraoka-Higashi 2, Fujisawa, Kanagawa, 251-8555, Japan.
  • 5 Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
  • 6 Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. kaneko.shin@cira.kyoto-u.ac.jp.
  • # Contributed equally.
PMID: 38834758 DOI: 10.1038/s42003-024-06297-0
Abstract

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.

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