ArticleCancer immunology, immunotherapy : CII2026
Intracranially injected chimeric antigen receptor T cells eradicate glioblastoma cells but have limited potential to persist in the brain in a syngeneic mouse model.
Article in Cancer immunology, immunotherapy : CII, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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