Background/Purpose: Treatment of systemic lupus erythematosus (SLE) typically necessitates long-term immunosuppression with hormones, immunosuppressants and biologics. CD19-targeting chimeric antigen receptor (CAR) T cells have shown excellent efficacy in a variety of autoimmune diseases including SLE, indicating that reset of aberrant autoimmunity via deep B-cell depletion is a promising strategy for achieving sustained long-lasting remission.

Methods: We evaluated 20 patients with active severe and refractory SLE that received 3 does infusion of allogenic CD19-targeting CAR-nature killing (NK) cells after preconditioning with cyclophosphamide and fludarabine. Long-term efficacy up to 12 months after CAR-NK cells infusion was assessed by utilizing the criteria of lupus low disease activity state (LLDAS) and the 2021 DORIS (definition of remission in SLE) definition of remission in SLE. Short- and long-term safety concerned adverse events including the cytokine release syndrome and infections were monitored.

Results: The median disease duration is 10 years (from 1 to 17 years). 1 patient received does level (DL), 1 patient received DL2, 5 patients received DL3, and 13 patients received DL4 CAR-NK cells infusion. The median follow-up was 5 months (range, 1 to 12). Reconstitution of B cells was observed in 2 to 3 months post CAR-NK cells therapy. Grade 1 cytokine release syndrome (fever only for a short of time) occurred in 2 patients, no other adverse events and infections were observed during and post the CAR-NK cells treatment. Of the 8 patients with more than 6 months of follow-up, 50.0 % (4/8) achieved DORIS remission and 75.0% (6/8) achieved LLDAS.

Conclusion: In this study, allogeneic CD19-targeting CAR-NK cell therapy for SLE exhibited excellent safety and could also achieve rapid and long-lasting remission of relapsed and refractory SLE, which will be a promising off-shelf and universal cell therapy for patients with SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/allogenic-cd19-car-nk-cells-therapy-in-refractory-systemic-lupus-erythematosus-an-open-label-single-arm-prospective-and-interventional-clinical-trial/