1. GD2 CAR T cells against human glioblastoma
- Author
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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., and Dominici, M.
- Subjects
CNS cancer ,cancer immunotherapy ,CAR T strategy ,glioblastoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Article ,RC254-282 - 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.
- Published
- 2021