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Abstract
Objectives This study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients with systemic lupus erythematosus (SLE) with lupus nephritis (LN).
Methods This is a single-arm open-label multicentre phase 1 study of BCMA and CD19-directed cCAR in patients suffering from SLE/LN with autoantibodies produced by B cells and plasma/long-lived plasma cells. In this clinical trial, we sequentially assigned biopsy-confirmed (classes III–V) LN patients to receive 3×106 cCAR cells/kg postcessation of all SLE medications and conditioning. The primary endpoint of safety and toxicity was assessed. Complete immune reset was indicated by B cell receptor (BCR) deep sequencing and flow cytometry analysis. Patient 11 (P11) had insufficient lymphocyte counts and was underdosed as compassionate use.
Results P1 and P2 achieved symptom and medication-free remission (MFR) from SLE and complete remission from lymphoma. P3–P13 (excluding P11) received an initial dose of 3×106 cCAR cells /kg and were negative for all autoantibodies, including those derived from long-lived plasma cells, 3 months post-cCAR and the complement returned to normal levels. These patients achieved symptom and MFR with post-cCAR follow-up to 46 months. Complete recovery of B cells was seen in 2–6 months post-cCAR. Mean SLE Disease Activity Index 2000 reduced from 10.6 (baseline) to 2.7 (3 months), and renal function significantly improved in 10 LN patients ≤90 days post-cCAR. cCAR T therapy was well tolerant with mild cytokine-release syndrome.
Conclusions Data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in patients with SLE.
- Autoimmune Diseases
- Lupus Nephritis
- Lupus Erythematosus, Systemic
Data availability statement
Data are available on reasonable request.
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Data availability statement
Data are available on reasonable request.
Footnotes
Handling editor Josef S Smolen
Correction notice This article has been corrected since it published Online First. Cy/Influenza has been corrected to Cy/Flu in the methods section and figure 1.
Contributors WW, SH, MWada, FL, MH, TL, CZ, NH, MingxiaWang, LD, YupoMa, YY, WZ and HZ designed the treatment and analysis. VMD, DS, MinWang, KP, GD and YuMa performed molecular analysis. RZ, YL, ZG, MH and FL collected clinical data. YL, YupoMa produced CAR T cells. SH, MWada performed clinical monitoring. WW, YupoMa and MH wrote the manuscript. YY is responsible for the overall content as the guarantor.
Funding The Natural Science Foundation of Guangdong Province (grant number 2021A1515011320) and Major scientific research project of basic and applied basic research in Guangdong Province (grant number B2022151523007).
Disclaimer The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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