CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis.
Med
; 5(6): 550-558.e2, 2024 Jun 14.
Article
en En
| MEDLINE
| ID: mdl-38554710
ABSTRACT
BACKGROUND:
Progressive multiple sclerosis (MS) is characterized by compartmentalized smoldering neuroinflammation caused by the proliferation of immune cells residing in the central nervous system (CNS), including B cells. Although inflammatory activity can be prevented by immunomodulatory therapies during early disease, such therapies typically fail to halt disease progression. CD19 chimeric antigen receptor (CAR)-T cell therapies have revolutionized the field of hematologic malignancies. Although generally considered efficacious, serious adverse events associated with CAR-T cell therapies such as immune effector cell-associated neurotoxicity syndrome (ICANS) have been observed. Successful use of CD19 CAR-T cells in rheumatic diseases like systemic lupus erythematosus and neuroimmunological diseases like myasthenia gravis have recently been observed, suggesting possible application in other autoimmune diseases.METHODS:
Here, we report the first individual treatment with a fully human CD19 CAR-T cell therapy (KYV-101) in two patients with progressive MS.FINDINGS:
CD19 CAR-T cell administration resulted in acceptable safety profiles for both patients. No ICANS was observed despite detection of CD19 CAR-T cells in the cerebrospinal fluid. In case 1, intrathecal antibody production in the cerebrospinal fluid decreased notably after CAR-T cell infusion and was sustained through day 64.CONCLUSIONS:
CD19 CAR-T cell administration in progressive MS resulted in an acceptable safety profile. CAR-T cell presence and expansion were observed in the cerebrospinal fluid without clinical signs of neurotoxicity, which, along with intrathecal antibody reduction, indicates expansion-dependent effects of CAR-T cells on CD19+ target cells in the CNS. Larger clinical studies assessing CD19 CAR-T cells in MS are warranted.FUNDING:
Both individual treatments as well the generated data were not based on external funding.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Inmunoterapia Adoptiva
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Antígenos CD19
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Receptores Quiméricos de Antígenos
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania