Post by Nadica (She/Her) on Jul 17, 2024 20:52:17 GMT
Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis - Published July 15, 2024
Not covid specific, but the therapeutic potential for covid is obvious (and gives me a bit of hope).
Highlights
•TyU19 is a genetically engineered, healthy donor-derived CD19-targeting CAR-T product
•TyU19 caused B cell depletion in three patients with refractory autoimmune diseases
•TyU19 alleviated severe skeletal muscle damage in a patient with refractory IMNM
•TyU19 reversed extensive fibrotic damage to critical organs in two patients with dcSSc
Summary
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.
Graphical abstract
Not covid specific, but the therapeutic potential for covid is obvious (and gives me a bit of hope).
Highlights
•TyU19 is a genetically engineered, healthy donor-derived CD19-targeting CAR-T product
•TyU19 caused B cell depletion in three patients with refractory autoimmune diseases
•TyU19 alleviated severe skeletal muscle damage in a patient with refractory IMNM
•TyU19 reversed extensive fibrotic damage to critical organs in two patients with dcSSc
Summary
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.
Graphical abstract