Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Cell

Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; National Key Laboratory for Immunity and Inflammation, Shanghai, China; School of Medicine, Tsinghua University, Beijing 100084, China; Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

Published: September 2024

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

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Source
http://dx.doi.org/10.1016/j.cell.2024.06.027DOI Listing

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