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.

GD2 CAR T cells against human glioblastoma / Prapa, M.; Chiavelli, C.; Golinelli, G.; Grisendi, G.; Bestagno, M.; Di Tinco, R.; Dall'Ora, M.; Neri, G.; Candini, O.; Spano, C.; Petrachi, T.; Bertoni, L.; Carnevale, G.; Pugliese, G.; Depenni, R.; Feletti, A.; Iaccarino, C.; Pavesi, G.; Dominici, M.. - In: NPJ PRECISION ONCOLOGY. - ISSN 2397-768X. - 5:1(2021), pp. 1-14. [10.1038/s41698-021-00233-9]

GD2 CAR T cells against human glioblastoma

Prapa M.;Chiavelli C.;Golinelli G.;Grisendi G.;Di Tinco R.;Dall'Ora M.;Candini O.;Spano C.;Petrachi T.;Bertoni L.;Carnevale G.;Pugliese G.;Depenni R.;Iaccarino C.;Pavesi G.;Dominici M.
2021

Abstract

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.
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GD2 CAR T cells against human glioblastoma / Prapa, M.; Chiavelli, C.; Golinelli, G.; Grisendi, G.; Bestagno, M.; Di Tinco, R.; Dall'Ora, M.; Neri, G.; Candini, O.; Spano, C.; Petrachi, T.; Bertoni, L.; Carnevale, G.; Pugliese, G.; Depenni, R.; Feletti, A.; Iaccarino, C.; Pavesi, G.; Dominici, M.. - In: NPJ PRECISION ONCOLOGY. - ISSN 2397-768X. - 5:1(2021), pp. 1-14. [10.1038/s41698-021-00233-9]
Prapa, M.; Chiavelli, C.; Golinelli, G.; Grisendi, G.; Bestagno, M.; Di Tinco, R.; Dall'Ora, M.; Neri, G.; Candini, O.; Spano, C.; Petrachi, T.; Bertoni, L.; Carnevale, G.; Pugliese, G.; Depenni, R.; Feletti, A.; Iaccarino, C.; Pavesi, G.; Dominici, M.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1256722
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