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<p>Glioblastoma multiforme (GBM) is among the most malignant primary brain tumors, necessitating the development of novel therapies. Intracranial injection of chimeric antigen receptor (CAR)-T cell therapy is effective against GBM. However, whether intracranially injected CAR-T cells persist in the brain for long periods is unclear. In this study, we established a syngeneic murine model of GBM by injecting GL261 murine GBM cells expressing human B7-H3. After confirming tumor engraftment, murine T cells transduced with CAR-targeting human B7-H3 were injected intratumorally. Reduced tumor burden and enhanced survival were observed in mice injected with B7-H3 CAR-T cells compared with those injected with control T cells. CAR-T cells were distinctly detected in the brain 1&#xa0;week after CAR-T cell injection, but disappeared 2&#xa0;weeks after injection. In the syngeneic mouse model, intracranially injected CAR-T cells have the potential to eradicate GBM but do not persist in the brain for long, suggesting that intracranial injections of CAR-T cells need to be repeatedly administered, as has been done in several clinical trials. It will be important to develop strategies to enhance persistence of CAR-T cells in the brain.</p>

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Intracranially injected chimeric antigen receptor T cells eradicate glioblastoma cells but have limited potential to persist in the brain in a syngeneic mouse model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Koki Murakami,
  • Noriyuki Kijima,
  • Hideki Kuroda,
  • Tetsuro Tachi,
  • Shunya Ikeda,
  • Kanji Nakagawa,
  • Yuki Wada,
  • Tatsuya Hagioka,
  • Naoko Hatanaka,
  • Ryuichi Hirayama,
  • Haruhiko Kishima,
  • Naoki Hosen

摘要

Glioblastoma multiforme (GBM) is among the most malignant primary brain tumors, necessitating the development of novel therapies. Intracranial injection of chimeric antigen receptor (CAR)-T cell therapy is effective against GBM. However, whether intracranially injected CAR-T cells persist in the brain for long periods is unclear. In this study, we established a syngeneic murine model of GBM by injecting GL261 murine GBM cells expressing human B7-H3. After confirming tumor engraftment, murine T cells transduced with CAR-targeting human B7-H3 were injected intratumorally. Reduced tumor burden and enhanced survival were observed in mice injected with B7-H3 CAR-T cells compared with those injected with control T cells. CAR-T cells were distinctly detected in the brain 1 week after CAR-T cell injection, but disappeared 2 weeks after injection. In the syngeneic mouse model, intracranially injected CAR-T cells have the potential to eradicate GBM but do not persist in the brain for long, suggesting that intracranial injections of CAR-T cells need to be repeatedly administered, as has been done in several clinical trials. It will be important to develop strategies to enhance persistence of CAR-T cells in the brain.