Epratuzumab

B cell acute lymphoblastic leukemia (B-ALL) is characterized by an accumulation of malignant precursor cells. Treatment consists of multiagent chemotherapy followed by allogeneic stem cell transplantation in high-risk patients. In addition, patients bearing the BCR-ABL1 fusion gene receive concomitant tyrosine kinase inhibitor (TKI) therapy. On the other hand, monoclonal antibody therapy is increasingly used in both clinical trials and real-world settings. The introduction of rituximab has improved the outcomes in CD20 positive cases...

Several investigational agents are under evaluation in systemic lupus erythematosus (SLE) clinical trials but quantitative frameworks to enable comparison of their efficacy to reference benchmark treatments are lacking. To benchmark SLE treatment effects and identify clinically important covariates, we developed a model-based meta-analysis (MBMA) within a latent variable model framework for efficacy end points and SLE composite end point scores (BILAG-based Composite Lupus Assessment and Systemic Lupus Erythematosus Responder Index) using aggregate-level data on approved and investigational therapeutics...

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune systemic disease with a wide range of clinical symptoms, complex development processes, and uncertain prognosis. The clinical treatment of SLE is mainly based on hormones and immunosuppressants. Research on novel therapy strategies for SLE has flourished in recent years, especially the emergence of new targeted drugs and natural products that can modulate related symptoms. This review discusses the current experience including B-cell targeted drugs (belimumab, tabalumab, blisibimod, atacicept, rituximab, ofatumumab, ocrelizumab, obexelimab, and epratuzumab), T-cell targeted drugs (abatacept, dapirolizumab, and inhibitor of syk and CaMKIV), cytokines targeted drugs (anifrolumab and sifalimumab), and natural products (curcumin, oleuropein, punicalagin, sulforaphane, icariin, apigenin, and resveratrol)...

INTRODUCTION: Systemic lupus erythematosus (SLE) is characterized by autoantibody expression and aberrant autoreactive B cells contribute to disease progression; therefore, B cell inhibition has been an attractive target for novel therapies. However, after more than two decades of research and over 40 randomized clinical trials, only one such therapy, belimumab, has been approved for use in SLE. AREAS COVERED: In this review, we discuss the evidence for B cell-targeted therapies in SLE and lupus nephritis...

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown aetiology, characterised by the production of auto-antibodies and formation of immune complexes against self-antigens and complement activation. This inflammatory response can lead to tissue infiltration and eventually, to organ damage.Patients with SLE invariably have periods of relapse and remission. Flares can occur even when the patient is on seemingly adequate treatment, which suggests that more effective therapies are necessary for the management of SLE...

Treatment of non-Hodgkin lymphoma (NHL) in general has improved over the years with the emergence of the monoclonal antibodies (MAB) therapy. NHL is divided into B cell NHL and T cell NHL. Treatment of NHL was based on the subtype of NHL and its staging. NHL is divided into aggressive and indolent NHL (iNHL). Subtypes of iNHL include: Follicular lymphoma (FL), Marginal zone lymphoma (MZL), Chronic lymphocytic leukemia/small-cell lymphocytic lymphoma (CLL/SLL), Gastric mucosa-associated lymphoid tissue (MALT) lymphoma, Lymphoplasmacytic lymphoma, Waldenström macroglobulinemia, Nodal marginal zone lymphoma (NMZL), Splenic marginal zone lymphoma (SMZL)...

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune condition for which there are limited licensed therapies. Clinical trial design is challenging in SLE due at least in part to imperfect outcome measures. Improved understanding of how disease activity changes over time could inform future trial design. The aim of this study was to determine whether distinct trajectories of disease activity over time occur in patients with active SLE within a clinical trial setting and to identify factors associated with these trajectories...

Immunotherapeutic agents play an increasingly important role in the treatment of B-cell malignancies. CD19 and CD20 are common targets for lymphoid malignancies, though patients who relapse have few therapeutic options remaining. CD22 is a cell surface sialoglycoprotein uniquely present on B-cells and regulates B-cell function and proliferation. Thus, it is an appealing therapeutic target for autoimmune disorders and B-cell malignancies. A variety of therapies targeting CD22 have been developed, including monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, chimeric antigen receptor T cells, and bispecific antibodies...

Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children with hematologic malignancies. A detailed literature review until January 2021 was conducted regarding pediatric patient populations treated with agents that target CD2 (alefacept), CD3 (bispecific T-cell engager [BiTE] blinatumomab), CD19 (denintuzumab mafodotin, B43, BiTEs blinatumomab and DT2219ARL, the immunotoxin combotox, and chimeric antigen receptor [CAR] T-cell therapies tisagenlecleucel and axicabtagene ciloleucel), CD20 (rituximab and biosimilars, 90 Y-ibritumomab tiuxetan, ofatumumab, and obinutuzumab), CD22 (epratuzumab, inotuzumab ozogamicin, moxetumomab pasudotox, BiTE DT2219ARL, and the immunotoxin combotox), CD25 (basiliximab and inolimomab), CD30 (brentuximab vedotin and iratumumab), CD33 (gemtuzumab ozogamicin), CD38 (daratumumab and isatuximab), CD52 (alemtuzumab), CD66b (90 Y-labelled BW 250/183), CD248 (ontuxizumab) and immune checkpoint inhibitors against CTLA-4 (CD152; abatacept, ipilimumab and tremelimumab) or with PD-1/PD-L1 blockade (CD279/CD274; atezolizumab, avelumab, camrelizumab, durvalumab, nivolumab and pembrolizumab)...

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease of unknown etiology, whose hallmark is the production of autoantibodies. B cells are promising targets for novel SLE therapies. In 2011, belimumab (Benlysta® ), a fully humanized monoclonal antibody inhibiting B-cell activation and proliferation, was the first medication in 50 years to be approved by the US Food and Drug Administration to treat adult SLE. This review discusses the current experience with B-cell-targeted therapies, including those targeting B-cell-surface antigens (rituximab, ocrelizumab, ofatumumab, obinutuzumab, obexelimab, epratuzumab, daratumumab), B-cell survival factors (belimumab, tabalumab, atacicept, blisibimod), or B-cell intracellular functions (ibrutinib, fenebrutinib, proteasome inhibitors), for the management of SLE...

Successful transplantation outcome is the final goal in most end stage and nonfunctional organs; however, despite using different therapeutic strategies, antibody-mediated rejection is still a big obstacle. B cells have a key role in transplant rejection by several functions, such as antibody production, antigen presenting, contribution in T cell activation, forming the germinal center, and tertiary lymphoid organs. Therefore, B cells modulation seems to be very crucial in transplant outcome. A double-edged sword function is considered for B cells during transplantation; On the one hand, antibody production against the transplanted organ induces antibody-mediated rejection...

B cell malignancies, such as B cell leukemia and lymphoma, have CD22 overexpression with ∼7% of patients. A short CD22 binding peptide (PV3) with a moderate affinity (Kd ∼ 9 μM) was identified by screening multiple peptide candidates determined through analysis of CD22-epratuzumab complex crystal structure. PV3 binding specificity was confirmed via competitive binding inhibition, then was used as the targeting moiety on CD22-targeted liposomal nanoparticle (TNPPV3) formulations. To maximize the potential therapeutic outcome of TNPPV3 formulation, nanoparticle design parameters, such as peptide hydrophilicity, ethylene glycol linker length, valency, and particle size were optimized for maximum selective cellular uptake by CD22+ malignant cancer cells...

Objective: Previous studies have shown that biologic agents out of the nine medicines might be beneficial for the treatment of SLE. The aim of this study was to evaluate the most effective medication of six biologic agents in treatment of SLE using network meta-analysis (NMA). The performance of these processes is ranked according to the results of this analysis. Methods: Multiple databases including PubMed, EMBASE and Cochrane Library was used to identify applicable articles and collect relevant data to analyzed by using STATA (13...

Systemic lupus erythematosus (SLE) is a remarkable and challenging autoimmune disorder that is characterized by a broad range of clinical manifestations, such as flares and remissions. Recently, the humanized anti-CD22 antibody epratuzumab for SLE has been extensively studied. The aim of the present study was to perform a meta-analysis on the findings of associated randomized controlled trials in order to evaluate the effects of epratuzumab on SLE. Data from publications in PubMed, EMBASE and the Cochrane Library were collected up to March 2017...

Follicular lymphoma (FL) patients treated with firstline R-CHOP who experience progression of disease (POD) within 2 years have a shorter survival than those who do not have POD within 2 years. Whether this observation holds for patients treated initially with biologic immunotherapy alone is unknown. We performed a retrospective analysis of 174 patients pooled from three frontline rituximab (R)-based nonchemotherapy doublet trials: R-galiximab (Anti-CD80, CALGB 50402), R-epratuzumab (Anti-CD22, CALGB 50701), and R-lenalidomide (CALGB 50803) to determine outcomes of early progressors and risk factors for early POD, defined as progression within 24 months from study entry...

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. There are three drugs licensed for the treatment of lupus: corticosteroids, hydroxychloroquine and belimumab. Immunosuppressants such as azathioprine, methotrexate and mycophenolate are also used. Despite these treatments there is still considerable morbidity. New treatments are needed for the management of active lupus. Epratuzumab a humanized IgG1 monoclonal antibody that targets CD22 resulting in selective B cell modulation that has been considered a potential treatment for SLE...

OBJECTIVES: To systematically review, and conduct a meta-analysis of steroid-sparing effect in, phase 3 randomized, placebo-controlled trials of biologic therapies for systemic lupus erythematosus (SLE). METHODS: Studies were identified by searching Medline (via Pubmed), EMBASE, CINAHL and SCOPUS databases, the Cochrane library, and clinicaltrials.gov. Adult human studies published in English in the last ten years (until 18/04/2017) were included. A random-effects meta-analysis comparing a common corticosteroid-reduction endpoint in the trials of rituximab, belimumab, tabalumab and epratuzumab in SLE, was conducted...

OBJECTIVE: EMBODY 1 (ClinicalTrials.gov identifier: NCT01262365) and EMBODY 2 (ClinicalTrials.gov identifier: NCT01261793) investigated the efficacy and safety of epratuzumab, a CD22-targeted humanized monoclonal IgG antibody, in patients with systemic lupus erythematosus (SLE). The studies showed no significant difference from placebo in primary or secondary clinical outcome measures but did demonstrate B cell-specific immunologic activity. The aim of this post hoc analysis was to determine whether epratuzumab had a different clinical efficacy profile in SLE patients with versus those without an associated diagnosis of Sjögren's syndrome (SS)...

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CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers. Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins. The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals...