CD19-targeted chimeric antigen receptor T cell therapy...

CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis - Published Mar 29, 2024

A new possible MS treatment with some possible application for other disorders (perhaps including long covid since viral persistence seems to play a role)

Highlights

•CD19 CAR-T cell therapy showed tolerable short-term safety in two patients with MS
•CAR-T cell expansion was observed in cerebrospinal fluid without neurotoxicity
•Intrathecal antibody production decreased after CAR-T cell infusion in one patient

Summary
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.