Chimeric antigen receptor engineered T-cell therapy for central nervous system lymphoma

Abstract

Central nervous system lymphoma (CNSL) includes primary and secondary subtypes. It is associated with poor prognosis even after aggressive therapies. Primary CNSL involves mainly the brain, eyes, leptomeninges and spinal cord, without evidence of systemic non-Hodgkin’s lymphoma (NHL). Secondary CNSL refers to involvement of the CNS secondary to systemic NHL. Chimeric antigen receptor T (CAR-T) cells are genetically engineered T-cells directed against tumor target antigens. CAR-T-cells have shown encouraging results in treating B-cell malignancies. Clinical data on CAR-T-cells in CNSL treatment are limited, because of concerns regarding the immunoprivileged status of the CNS and the possibility of immune effector cell-associated neurotoxicity syndrome. Clinical trials on CAR-T therapy for CNSL are increasingly being conducted to evaluate its efficiency and safety since CAR-T-cells have been detected in the cerebrospinal fluid from a patient with PMBCL who received CAR-T-cell therapy. Current data suggest that CAR-T-cells are an emerging therapeutic modality for CNSL with clinical benefits and acceptable adverse effects. However, whether CAR-T therapy may be a promising therapeutic avenue remains controversial, because evidence from large-scale randomized clinical trials remains lacking. Herein, we provide a review of existing clinical data on CAR-T-cell therapy for CNSL, discuss the limitations of CAR-T-cells in CNSL treatment and hypothesize strategies to overcome these challenges.