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

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...

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Main Authors: Leonardo Palazzo, Valentina Pieri, Giulia Berzero, Massimo Filippi
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Brain Sciences
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Online Access:https://www.mdpi.com/2076-3425/14/12/1220
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author Leonardo Palazzo
Valentina Pieri
Giulia Berzero
Massimo Filippi
author_facet Leonardo Palazzo
Valentina Pieri
Giulia Berzero
Massimo Filippi
author_sort Leonardo Palazzo
collection DOAJ
description 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.
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spelling doaj-art-2fd7cc9683bc492aa2303356795b3cf52025-08-20T02:56:06ZengMDPI AGBrain Sciences2076-34252024-11-011412122010.3390/brainsci14121220CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging NeurotoxicitiesLeonardo Palazzo0Valentina Pieri1Giulia Berzero2Massimo Filippi3Neurology Unit, IRCCS Ospedale San Raffaele, 20132 Milan, ItalyNeurology Unit, IRCCS Ospedale San Raffaele, 20132 Milan, ItalyNeurology Unit, IRCCS Ospedale San Raffaele, 20132 Milan, ItalyNeurology Unit, IRCCS Ospedale San Raffaele, 20132 Milan, ItalyThe 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.https://www.mdpi.com/2076-3425/14/12/1220CAR-T cellsCNS tumoursneurotoxicityICANSTIAN
spellingShingle Leonardo Palazzo
Valentina Pieri
Giulia Berzero
Massimo Filippi
CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities
Brain Sciences
CAR-T cells
CNS tumours
neurotoxicity
ICANS
TIAN
title CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities
title_full CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities
title_fullStr CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities
title_full_unstemmed CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities
title_short CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities
title_sort car t cells for the treatment of central nervous system tumours known and emerging neurotoxicities
topic CAR-T cells
CNS tumours
neurotoxicity
ICANS
TIAN
url https://www.mdpi.com/2076-3425/14/12/1220
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AT valentinapieri cartcellsforthetreatmentofcentralnervoussystemtumoursknownandemergingneurotoxicities
AT giuliaberzero cartcellsforthetreatmentofcentralnervoussystemtumoursknownandemergingneurotoxicities
AT massimofilippi cartcellsforthetreatmentofcentralnervoussystemtumoursknownandemergingneurotoxicities