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Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Rituximab is a monoclonal antibody against CD20, which exerts its effect by selectively depleting CD20+ B cells. It is indicated in the use of rheumatoid arthritis and in lymphomas. Kimby et al. reported on the unintentional use of rituximab in a patient with recurrent NHL in the first trimester of pregnancy (101). She delivered a normal, healthy infant without evidence of hematologic or immunologic abnormalities. Other reports of first-trimester administration have also demonstrated no teratogenic or immunologic effects on the fetus or neonate (102). Pellkofer et al. reported on the use of rituximab for the treatment of neuromyelitis optica 1 week prior to conception (103). The patient delivered a healthy infant with normal development at 15 months. Another patient with idiopathic thrombocytopenic purpura was treated with rituximab weekly for 4 weeks in the third trimester (104). A healthy infant was born 1 month after the last administration of the drug. However, the child had no detectable B lymphocytes. Six months following delivery, her B-lymphocyte counts were normal, and at 10 months, she had normal vaccination titers. Other authors have confirmed this finding of significant rituximab concentrations in the neonate, transient B-lymphocyte depletion, quick recovery, and an absence of immunologic or other neonatal consequences (105–107).
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
CD20 is widely expressed on B cells, from early in their existence to later differentiation, but is absent on terminally differentiated plasma cells. The antigen does not modulate, shed, or internalize. Although the function of CD20 is not entirely known, it appears to play a role in Ca2+ influx across plasma membranes, maintaining intracellular Ca2+ concentration, and allowing activation of B cells. It has been found to have a general regulatory effect on cell cycle and on immune-receptor expression. Experiments in primates have shown that anti-CD20 treatment can reduce peripheral B cells by up to 98%, and peripheral lymph node and bone marrow B cells by up to 95%. Conversely, in multiple myeloma in humans, treatment with rituximab fails to deplete circulating CD20+ B cells or plasma cells, even after up to four cycles of treatment, and B cells can actually increase in some patients.
Anti-CD20 Monoclonal Antibody Treatment in Follicular Lymphoma and Chronic Lymphocytic Leukemia
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
The CD20 molecule is a 33 kDa cell surface antigen found almost exclusively on B cells. It is a membrane-embedded phosphoprotein composed structurally of four transmembrane domains, two extracellular loops, and cytoplasmic N- and C-terminal domains [5]. It was first characterized in 1980 as the first antigen specific to human B lymphocytes. CD20 was initially found to be present on over 95% of B cells from blood and lymphoid organs, and 9% of peripheral blood mononuclear cells. Removal of the antigen-expressing cells from the peripheral blood eliminated the cell population destined to differentiate into immunoglobulin-producing plasma cells after stimulation with pokeweed mitogen [6]. Later studies described the developmentally regulated and lineage-specific nature of CD20 expression, showing it to be expressed starting at the pre-B stage but lost after differentiation to plasma cells [7, 8]. Most notably, CD20 was also found to be present on the surface of malignant B cells, including chronic lymphocytic leukemia and the majority of B-cell lymphomas [9].
Biological therapies for myasthenia gravis
Published in Expert Opinion on Biological Therapy, 2023
Akiyuki Uzawa, Kimiaki Utsugisawa
Rituximab is a monoclonal antibody that acts against CD20, which is selectively expressed by specific B cells. The most common treatment regimen of rituximab involves 375 mg/m2 IV administration per week for 4 weeks. A systematic review revealed that response to rituximab was significantly better in patients with MuSK-antibody-positive MG. Overall, 72% of patients with MuSK-antibody-positive MG achieved an improved status, whereas only 30% of patients with AChR-antibody-positive MG achieved an improved status [26]. In the phase 2 clinical trial of rituximab for AChR-antibody-positive generalized MG, the primary endpoint, i.e. steroid-sparing outcome, was achieved in 60% of patients receiving rituximab and 56% of those receiving placebo, suggesting that rituximab provides less benefit on the assessed endpoints, although it was safe and well-tolerated [27]. Recently, it has been reported that a single dose of 500 mg rituximab is associated with a greater incidence of minimal MG manifestations (defined by a QMG score of ≤4 with a daily prednisolone dose of ≤10 mg and no rescue treatment) and a reduced need for rescue medication in patients with early-phase generalized MG (96% of AChR-antibody-positive cases) compared to placebo [28]. The efficacy of rituximab in AChR-positive MG cannot be confirmed at present, and this warrants further analysis.
B cell depletion and inhibition in systemic lupus erythematosus
Published in Expert Review of Clinical Immunology, 2023
Eugene Krustev, Ann E. Clarke, Megan R.W. Barber
Targeting B cell-expressed surface molecules using highly selective monoclonal antibodies (mAbs) can induce B cell depletion and is a well-studied therapeutic target in SLE. CD20 is a surface protein that is widely expressed on B cells during multiple stages of development; however, it is not expressed on pro-B cells and plasma cells. Although not fully understood, CD20 likely functions as a calcium channel [11,12]. Rituximab, obinutuzumab, ocrelizumab, and ofatumumab are all anti-CD20 mAbs that have been tested in SLE. CD22 is another cell surface molecule that is primarily expressed on B cells, but not on plasma cells or pro-B cells [13]. CD22 functions as a regulatory molecule and inhibits B cell overactivation [14]. A single anti-CD22 mAb, epratuzumab, has been tested in SLE. Lastly, obexelimab, a CD19-targeted agent, has also been tested in SLE.
Drug safety in thyroid eye disease – a systematic review
Published in Expert Opinion on Drug Safety, 2022
Jan Wolf, Kamila I. Mitka, Alicja Hubalewska-Dydejczyk, Irene Krämer, George J Kahaly
Rituximab (RTX) is a humanized, chimeric anti-CD20 monoclonal antibody, the antigen-binding region is derived from a mouse antibody. Three potential immunosuppressive mechanisms have been described: (i) reduction of B-cell antigen-presentation, (ii) decreased production of pro-inflammatory cytokines, and (iii) reduction of pathogenic autoantibody generation. The CD20 molecule (CD20) is expressed on the surface of B-cells only and is present since the stage of pre, mature, and memory B-cells. However, CD20 is not expressed on stem cells, B-cell precursors, and plasma cells. B-cell activation and differentiation is inhibited after RTX binds to CD20 – this leads to the specific elimination of B-cells without affecting their regeneration and immunoglobulin production. As a result, the B-cell population declines, the B-cell antigen-presenting capacity is reduced, the T-cell activation is decreased, and the inflammatory process halts. Although the RTX mechanism of action process does not correlate directly with plasma cells – however, elimination of plasma cell precursors by RTX can reduce the production of pathogenic autoantibodies. Reduction of TSHR-Ab levels was noted without correlating with peripheral B-cell depletion or clinical response in patients with GD and/or TED [6,94–96].