Article
作者: Li, Fugui ; Shah, Darshi ; Pinz, Kevin ; He, Shanzhi ; DeStefano, Vincent M ; Zhang, Wenli ; Liang, Yingwen ; Zhang, Hongyu ; Wang, Min ; Hagag, Nabil ; Zeng, Ronghao ; Ma, Yu ; Ma, Yupo ; Wada, Masayuki ; Lan, Ting ; Guo, Zhencong ; Yuan, Yong ; Zou, Chanjuan ; Deener, Greg ; Ding, Ling ; Wang, Weijia ; Hong, Ming ; Wang, Mingxia
ObjectivesThis 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 3×10
6
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 3×10
6
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.
ConclusionsData suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in patients with SLE.