GD2 CAR T cells against human glioblastoma

Autor: 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.
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: npj Precision Oncology, Vol 5, Iss 1, Pp 1-14 (2021)
NPJ Precision Oncology
Popis: 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.
Databáze: OpenAIRE