Neutralizing IFNγ Improves Safety without Compromising Efficacy of CAR-T Cell Therapy in B-cell Malignancies

Chimeric antigen receptor T (CAR-T) cell therapy shows promise for treating B-cell malignancies, but severe side effects like cytokine release syndrome (CRS) and neurotoxicity limit its use. This study uses a humanized mouse model to demonstrate that IFNγ neutralization with emapalumab, a clinically approved monoclonal antibody, mitigates these toxicities without affecting the anti-leukemic efficacy of CAR-T cells. Emapalumab reduces inflammation, preventing brain damage, while preserving the ability of CD19-targeting CAR-T cells to eradicate CD19⁺ lymphomas. This suggests a potential for combination therapy using emapalumab and CAR-T cells.

Simona Manni, Francesca Del Bufalo, Pietro Merl, Domenico Alessandro Silvestri, Marika Guercio, Simona Caruso, Sofia Reddel, Laura Iaffaldano, Michele Pezzella, Stefano Di Cecca, Matilde Sinibaldi, Alessio Ottaviani, Maria Cecilia Quadricaccia, Marisaol Aurigemma, Andrea Sarcinelli, Roselia Ciccone, Zeinab Abbaszadeh, Manuela Ceccarelli, Rita De Vito, Maria Chiara Lodi, Maria Giuseppina Cefalo, Angela Mastronuzzi, Biagio De Angelis, Franco Locatelli, Concetta Quintarelli