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. 2021 Dec;17(6):2120-2123.
doi: 10.1007/s12015-021-10251-6. Epub 2021 Aug 30.

Treatment of Systemic Lupus Erythematosus using BCMA-CD19 Compound CAR

Wenli Zhang  1 , Jia Feng  1 , Andrew Cinquina  2 , Qingwen Wang  3 , Haichan Xu  1 , Qian Zhang  1 , Lihua Sun  1 , Qi Chen  1 , Lei Xu  1 , Kevin Pinz  2 , Masayuki Wada  2 , Xun Jiang  2 , Yupo Ma  4 , Hongyu Zhang  5
Affiliations

Treatment of Systemic Lupus Erythematosus using BCMA-CD19 Compound CAR

Wenli Zhang et al. Stem Cell Rev Rep. 2021 Dec.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Y.M. is a cofounder of iCell Gene Therapeutics, LLC. All other authors report no conflict of interest.

Figures

Fig. 1
Fig. 1
Mechanism of cCAR. The cCAR construct is a two-unit CAR composed of a complete BCMA-CAR fused to a complete CD19-CAR (also called CD19B-CAR) by a self-cleaving P2A peptide, enabling independent expression of both CAR receptors separately on the T cell surface. This allows cCAR to target two long-lived antibody-producing “root cells” – CD19 + memory B-cells and BCMA + plasma cells
Fig. 2
Fig. 2
SLE remains inactive in patient after cCAR T cell injection (A) After the infusion of 5.3 × 106/kg cCAR T cells, the first peak of cCAR T cells in the peripheral blood accrued at 7 days after cCAR infusion, and marked expansion of cCAR T cells was seen during the two months of treatment. Measured in percentage of total lymphocytes by flow cytometry analysis. (B) The number of B cells and CD3 + CD8 + cells were also monitored during the treatment. CD3 + CD8 + cells reached their first peak 7 days after cCAR treatment at 267 cells/μL and a second peak 2 months after treatment at 595 cells/μL. B cell numbers remained undetectable for three months post-cCAR and returned to normal levels 9 months after cCAR therapy. Measured in 106 cells/L. (C) Complement levels of C3 and C4 were measured before and after cCAR treatment. Levels remained normal despite discontinuation of immunosuppressive therapy. Normal range for C3 and C4 are 0.8–1.6 g/L and 0.16–0.48 g/L, respectively. (D) Anti-nuclear antibody (ANA) titers were measured before and after cCAR treatment. Levels of nuclear ANAs were highly elevated prior to treatment, declined in the first few weeks, and remained undetectable after 12 weeks. Granular and cytoplasmic ANA had similar responses. (E) Immunoglobulin levels of IgG, IgM, and IgA were measured before and after cCAR therapy. All immunoglobulin levels decreased demonstrating a decrease in B cells and immunoglobulin-producing plasma cells. (F) Representation of the decline in immunoglobins from (E) as percent reduction from their levels before cCAR treatment
See this image and copyright information in PMC

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