Emerging B-Cell Therapies in Systemic Lupus Erythematosus

Bag-Ozbek, Ayse; Hui-Yuen, Joyce

doi:10.2147/tcrm.s252592

Cited by 49 publications

(33 citation statements)

References 85 publications

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“…In vitro experiments show that Daratumumab (an anti-CD38 monoclonal antibody) removes plasma cells and plasmablasts in PBMC of RA patients in a dose-dependent manner ( 119 ). Studies have reported that daratumumab has been successful in the treatment of 2 patients with refractory systemic lupus erythematosus, but the efficacy and safety of Daratumumab in the treatment of RA patients still need to be confirmed ( 120 ). Abatacept (CTLA-4Ig) has been successfully used to treat autoimmune diseases and has been approved for the treatment of RA.…”

Section: The Prospect Of Treating Ra With B Cells As a Targetmentioning

confidence: 99%

B Cells in Rheumatoid Arthritis：Pathogenic Mechanisms and Treatment Prospects

et al. 2021

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Rheumatoid arthritis (RA) is a common, chronic, systemic autoimmune disease, and its clinical features are the proliferation of joint synovial tissue, the formation of pannus and the destruction of cartilage. The global incidence of RA is about 1%, and it is more common in women. The basic feature of RA is the body’s immune system disorders, in which autoreactive CD4+T cells, pathogenic B cells, M1 macrophages, inflammatory cytokines, chemokines and autoantibodies abnormally increase in the body of RA patients B cell depletion therapy has well proved the important role of B cells in the pathogenesis of RA, and the treatment of RA with B cells as a target has also been paid more and more attention. Although the inflammatory indicators in RA patients receiving B-cell depletion therapy have been significantly improved, the risk of infection and cancer has also increased, which suggests that we need to deplete pathogenic B cells instead of all B cells. However, at present we cannot distinguish between pathogenic B cells and protective B cells in RA patients. In this review, we explore fresh perspectives upon the roles of B cells in the occurrence, development and treatment of RA.

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Section: The Prospect Of Treating Ra With B Cells As a Targetmentioning

confidence: 99%

B Cells in Rheumatoid Arthritis：Pathogenic Mechanisms and Treatment Prospects

et al. 2021

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“…These other agents were a recombinant soluble TACI-Fc (sTACI-Fc) decoy receptor that binds APRIL and BAFF at 6.4 nM and 160 pM respectively (Wu et al, 2000), as well as an antibody against BAFF ( α BAFF Ab) with a K D of 0.995 nM and no reported binding to APRIL (Shin et al, 2018). The clinical versions of both molecules are currently used for the treatment of various B cell related autoimmune diseases (Bag-Ozbek and Hui-Yuen, 2021; Barratt et al, 2020; Lee and Amengual, 2020). We performed an in vivo head-to-head comparison study evaluating the antitumor efficacy of sBCMA-Fc V3, sTACI-Fc, α BAFF Ab and wild-type sBCMA-Fc in SU-DHL-6 DLBCL tumors.…”

Section: Resultsmentioning

confidence: 99%

Developing High-Affinity Decoy Receptor Optimized for Multiple Myeloma and Diffuse Large B Cell Lymphoma Treatment

Miao

Cenik

Jiang

et al. 2021

Preprint

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B-cell maturation antigen (BCMA) is critical for the viability of Multiple Myeloma (MM) tumor cells and targeting BCMA poses a remarkable opportunity as a potential therapeutic in this cancer. Recent approval of BCMA directed CAR-T and Antibody-Drug-Conjugates (ADCs) have revolutionized MM treatment landscape. Despite such clinical success, treatment resistance and dose limiting toxicity remain as major clinical challenges. Using ribosome profiling, we established a molecular link between BCMA signaling inhibition and protein translation machinery. In addition, BCMA signaling alters the translation efficiency of a transcriptional regulator ATMIN without changing the total mRNA transcript level. Furthermore, ATMIN can transcriptionally regulate IL-6, a critical survival factor for MM. To inhibit the BCMA signaling pathway, we devised both genetic knockdown strategy and pharmacological inhibition by using a soluble BCMA decoy receptor fusion protein (sBCMA-Fc) to trap both of its ligands, APRIL and BAFF. We demonstrated that treatment of MM tumor cells with sBCMA-Fc inhibits tumor progression in numerous in vivo and syngenic PDX tumors models without significant adverse effects. Furthermore, the addition of sBCMA-Fc treatment can restore bortezomib sensitivity in previously bortezomib resistant MM tumors, further adding to its therapeutic value in the treatment of relapse /refractory MM patients. Inhibiting BCMA signaling through neutralization of its ligands APRIL and BAFF with a sBCMA-Fc fusion protein represents a safe and efficacious treatment strategy for the treatment of relapse and refractory MM.

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“…In mycobacterial infections due to anti-IFN-γ auto-antibodies, another phenocopy of an inborn error of immunity, rituximab has been used with success [ 69 – 73 ]. Depletion of plasmablasts can be achieved by antibodies targeting CD38 (e.g., daratumumab); the latter has been successfully used to treat multiple myeloma [ 74 ], autoimmune cytopenias [ 75 ], autoimmune organ diseases [ 76 , 77 ], and infection due to auto-Abs to cytokines [ 78 ]. These depletive therapies have not been studied as acute treatment for COVID-19 in the context of RCT or, to our knowledge, even published as case reports.…”

Section: B Cell and Plasmablast Depletion And Btk Inhibition: How About Covid?mentioning

confidence: 99%