학술논문
GD2 CAR T cells against human glioblastoma
Document Type
article
Author
Malvina Prapa; Chiara Chiavelli; Giulia Golinelli; Giulia Grisendi; Marco Bestagno; Rosanna Di Tinco; Massimiliano Dall’Ora; Giovanni Neri; Olivia Candini; Carlotta Spano; Tiziana Petrachi; Laura Bertoni; Gianluca Carnevale; Giuseppe Pugliese; Roberta Depenni; Alberto Feletti; Corrado Iaccarino; Giacomo Pavesi; Massimo Dominici
Source
npj Precision Oncology, Vol 5, Iss 1, Pp 1-14 (2021)
Subject
Language
English
ISSN
2397-768X
Abstract
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.