The advent of chimeric antigen receptor (CAR)‑T cells has recently changed the prognosis of relapsing/refractory diffuse large B‑cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell‑Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood–brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms, seizures, and diffuse brain oedema. The tremendous oncological efficacy of CAR‑T cells observed in systemic B‑cell malignancies is leading to their growing use in patients with primary or secondary central nervous system (CNS) lymphomas and in patients with solid tumours, including several CNS cancers. Early studies conducted in adult and paediatric patients with solid CNS tumours reported a distinct profile of neurotoxicity referred to as Tumour inflammation‑associated neurotoxicity (TIAN), corresponding to local inflammation at the tumour site manifesting with focal neurological deficits or mechanical complications (e.g., obstructive hydrocephalus). The present review summarises available data on the efficacy and safety of CAR‑T cells for solid and haematological CNS malignancies, emphasising known and emerging phenotypes, ongoing challenges, and future perspectives.

CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities / Palazzo, Leonardo; Pieri, Valentina; Berzero, Giulia; Filippi, Massimo. - In: BRAIN SCIENCES. - ISSN 2076-3425. - 14:12(2024). [10.3390/brainsci14121220]

CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities

Palazzo, Leonardo
Primo
;
Pieri, Valentina
Secondo
;
Berzero, Giulia
Penultimo
;
Filippi, Massimo
Ultimo
2024-01-01

Abstract

The advent of chimeric antigen receptor (CAR)‑T cells has recently changed the prognosis of relapsing/refractory diffuse large B‑cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell‑Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood–brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms, seizures, and diffuse brain oedema. The tremendous oncological efficacy of CAR‑T cells observed in systemic B‑cell malignancies is leading to their growing use in patients with primary or secondary central nervous system (CNS) lymphomas and in patients with solid tumours, including several CNS cancers. Early studies conducted in adult and paediatric patients with solid CNS tumours reported a distinct profile of neurotoxicity referred to as Tumour inflammation‑associated neurotoxicity (TIAN), corresponding to local inflammation at the tumour site manifesting with focal neurological deficits or mechanical complications (e.g., obstructive hydrocephalus). The present review summarises available data on the efficacy and safety of CAR‑T cells for solid and haematological CNS malignancies, emphasising known and emerging phenotypes, ongoing challenges, and future perspectives.
2024
CAR-T cells
CNS tumours
neurotoxicity;
ICANS
TIANS
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/173461
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