Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma

Chiara Chiavelli; Malvina Prapa; Giulia Rovesti; Marco Silingardi; Giovanni Neri; Giuseppe Pugliese; Lucia Trudu; Massimiliano Dall'Ora; Giulia Golinelli; Giulia Grisendi; Jonathan Vinet; Marco Bestagno; Carlotta Spano; Roberto Vito Papapietro; Roberta Depenni; Katia Di Emidio; Anna Pasetto; Daniela Nascimento Silva; Alberto Feletti; Silvia Berlucchi; Corrado Iaccarino; Giacomo Pavesi; Massimo Dominici

doi:10.1038/s41698-024-00506-z

Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma

NPJ Precis Oncol. 2024 Feb 1;8(1):26. doi: 10.1038/s41698-024-00506-z.

Authors

Chiara Chiavelli^#¹, Malvina Prapa^#¹, Giulia Rovesti^{1

2

3}, Marco Silingardi^{1

2}, Giovanni Neri^{1

2}, Giuseppe Pugliese^{1

3

4}, Lucia Trudu^{1

2

3}, Massimiliano Dall'Ora⁵, Giulia Golinelli^{1

6}, Giulia Grisendi¹, Jonathan Vinet⁷, Marco Bestagno⁸, Carlotta Spano⁹, Roberto Vito Papapietro³, Roberta Depenni³, Katia Di Emidio³, Anna Pasetto^{10

11}, Daniela Nascimento Silva¹¹, Alberto Feletti¹², Silvia Berlucchi¹³, Corrado Iaccarino¹³, Giacomo Pavesi^#¹³, Massimo Dominici^#^{14

15}

Affiliations

¹ Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.
² Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.
³ Department of Oncology and Hematology, University-Hospital of Modena and Reggio Emilia, Modena, Italy.
⁴ Leucid Bio Ltd., Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
⁵ Evotec (Modena) Srl, Medolla, Modena, Italy.
⁶ Center for Cellular Immunotherapies, Perelman School of Medicine, and Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA.
⁷ Centro Interdipartimentale Grandi Strumenti (CIGS), University of Modena and Reggio Emilia, Modena, Italy.
⁸ International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
⁹ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
¹⁰ Section for Cell Therapy, Radiumhospitalet, Oslo University Hospital, Oslo, Norway.
¹¹ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
¹² Department of Neurosciences, Biomedicine and Movement Sciences, Neurosurgery Unit, University of Verona, Verona, Italy.
¹³ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia - Division of Neurosurgery, Department of Neurosciences, University-Hospital of Modena and Reggio Emilia, Modena, Italy.
¹⁴ Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy. [email protected].
¹⁵ Department of Oncology and Hematology, University-Hospital of Modena and Reggio Emilia, Modena, Italy. [email protected].

^# Contributed equally.

Abstract

Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients.