Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies

Neurotoxicity is an important and common complication of chimeric antigen receptor-T cell therapies. Acute neurologic signs and/or symptoms occur in a significant proportion of patients treated with CD19-directed chimeric antigen receptor-T cells for B-cell malignancies. Clinical manifestations incl...

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Vydané v:	CNS drugs Ročník 32; číslo 12; s. 1091 - 1101
Hlavní autori:	Gust, Juliane, Taraseviciute, Agne, Turtle, Cameron J.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Cham Springer International Publishing 01.12.2018 Springer Nature B.V
Predmet:	Animal models Antigens Antigens, CD19 - metabolism Arthritis Blood-brain barrier Brain cancer CD19 antigen Cell activation Cell therapy Cerebrospinal fluid Chimeric antigen receptors Clinical trials Corticosteroids Cytokines Cytokines - blood Cytokines - cerebrospinal fluid Edema FDA approval Headache Humans Immunologic Factors - therapeutic use Immunotherapy Immunotherapy, Adoptive - methods Interleukin 6 Leading Article Leukemia Lymphocytes Lymphocytes B Lymphocytes T Lymphoma Medicine Medicine & Public Health Multiple myeloma Neurology Neurosciences Neurotoxicity Neurotoxicity Syndromes - epidemiology Neurotoxicity Syndromes - immunology Neurotoxicity Syndromes - metabolism Neurotoxicity Syndromes - therapy Pediatrics Pharmacotherapy Psychiatry Psychopharmacology Receptors, Antigen, T-Cell - metabolism Seizures Traumatic brain injury Young adults United States > US
ISSN:	1172-7047, 1179-1934, 1179-1934
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Popis
Shrnutí:	Neurotoxicity is an important and common complication of chimeric antigen receptor-T cell therapies. Acute neurologic signs and/or symptoms occur in a significant proportion of patients treated with CD19-directed chimeric antigen receptor-T cells for B-cell malignancies. Clinical manifestations include headache, confusion, delirium, language disturbance, seizures and rarely, acute cerebral edema. Neurotoxicity is associated with cytokine release syndrome, which occurs in the setting of in-vivo chimeric antigen receptor-T cell activation and proliferation. The mechanisms that lead to neurotoxicity remain unknown, but data from patients and animal models suggest there is compromise of the blood–brain barrier, associated with high levels of cytokines in the blood and cerebrospinal fluid, as well as endothelial activation. Corticosteroids, interleukin-6-targeted therapies, and supportive care are frequently used to manage patients with neurotoxicity, but high-quality evidence of their efficacy is lacking.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	1172-7047 1179-1934 1179-1934
DOI:	10.1007/s40263-018-0582-9