npj Precision Oncology (Oct 2021)

GD2 CAR T cells against human glioblastoma

  • 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

DOI
https://doi.org/10.1038/s41698-021-00233-9
Journal volume & issue
Vol. 5, no. 1
pp. 1 – 14

Abstract

Read online

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.