Neutralizing IFNγ improves safety without compromising efficacy of CAR-T cell therapy in B-cell malignancies.

ABSTRACT: Chimeric antigen receptor T (CAR-T) cell therapy may achieve long-lasting remission in patients with B-cell malignancies not responding to conventional therapies. However, potentially severe and hard-to-manage side effects, including cytokine release syndrome (CRS), neurotoxicity and macrophage activation syndrome, and the lack of pathophysiological experimental models limit the applicability and development of this form of therapy. Here we present a comprehensive humanized mouse model, by which we show that IFNγ neutralization by the clinically approved monoclonal antibody, emapalumab, mitigates severe toxicity related to CAR-T cell therapy. We demonstrate that emapalumab reduces the pro-inflammatory environment in the model, thus allowing control of severe CRS and preventing brain damage

SUBMITTER: Manni S 

PROVIDER: S-EPMC10256701 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature