GD2 CAR T cells against human glioblastoma

Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in...

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Veröffentlicht in:NPJ precision oncology 2021-10, Vol.5 (1), p.93-93, Article 93
Hauptverfasser: Prapa, Malvina, Chiavelli, Chiara, Golinelli, Giulia, Grisendi, Giulia, Bestagno, Marco, Di Tinco, Rosanna, Dall’Ora, Massimiliano, Neri, Giovanni, Candini, Olivia, Spano, Carlotta, Petrachi, Tiziana, Bertoni, Laura, Carnevale, Gianluca, Pugliese, Giuseppe, Depenni, Roberta, Feletti, Alberto, Iaccarino, Corrado, Pavesi, Giacomo, Dominici, Massimo
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Sprache:eng
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Zusammenfassung:Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma potentially opening a new therapeutic option for a still incurable cancer.
ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-021-00233-9