CAR T-cell associated neurotoxicity: Mechanisms, clinicopathologic correlates, and future directions
A partir de données cliniques et pré-cliniques, cette étude analyse les neurotoxicités des immunothérapies à base de lymphocytes CAR-T et propose des pistes pour prévenir et traiter ces neurotoxicités
Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary new form of immunotherapy for the treatment of hematologic malignancies. The two primary toxicities associated with CAR T-cell therapy include cytokine release syndrome (CRS) and neurotoxicity (NT). CRS is generally self-limited but high-grade toxicities like hypotension and hypoxemia can be managed with agents that block the effects of IL-6, like tocilizumab, and/or corticosteroids. While CAR-T cell therapy-associated NT is a well-described clinical phenomenon, its pathophysiology remains inadequately understood; treatments and preventive strategies remain elusive. Animal models and clinical trial experience suggest the centrality of monocytes, endothelial dysfunction, and the blood brain barrier in the development of CAR T-cell associated NT. Here we report what is known from pre-clinical models, clinical trials, and histopathologic studies regarding the pathophysiology of NT, predictors of its incidence, and potential targets for the treatment and prevention of NT.
Journal of the National Cancer Institute , résumé, 2018