Mechanism of action of rituximab

Cerny, Thomas; Borisch, Bettina; Introna, Martino; Johnson, Peter W.; Rose, Andrea L.

doi:10.1097/00001813-200211002-00002

Cited by 187 publications

(113 citation statements)

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“…S4), suggesting some potential common mechanisms for both types of resistance to BMS-536924. These genes are all somehow involved in drug resistance (43)(44)(45); further study of their roles in resistance to BMS-536924 is warranted.…”

Section: Discussionmentioning

confidence: 99%

The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors

et al. 2008

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Section: Discussionmentioning

confidence: 99%

The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors

et al. 2008

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“…Although very long-term data for children are lacking, B-cell recovery starts ϳ6 months after the completion of treatment and typically normalizes by 12 months, and serum Ig levels usually remain normal or slightly reduced. 1 Immunoreactivity to rituximab is uncommon.…”

Section: Discussionmentioning

confidence: 99%

“…1 Rituximab was approved by the US Food and Drug Administration in 1997 to treat B-cell non-Hodgkin's lymphomas 2 but has been used offlabel for the treatment of several types of autoimmune disorders among children and adults, such as autoimmune hemolytic anemia, 3 idiopathic autoimmune thrombocytopenia, 4 rheumatoid arthritis, 5 lupus, 6 autoimmune neuropathy, 7 and Wegener's granulomatosis. 8 Rituximab seems ideal for the study and treatment of childhood opsoclonus-myoclonus syndrome (OMS), a serious neurologic disorder in need of more effective therapy.…”

mentioning

confidence: 99%

Immunologic and Clinical Responses to Rituximab in a Child With Opsoclonus-Myoclonus Syndrome

et al. 2005

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“…[5][6][7][8] Remarkably, given its widespread use, we still have a relatively poor understanding of the nature of rituximab binding to B cells and how this mAb actually mediates its therapeutic effects in vivo. 3,[9][10][11][12][13][14][15] There are currently few well-characterized, highly specific reagents to detect rituximab. Previous reagents have been polyclonal and directed either to the rituximab idiotype (Id) 16,17 or the remaining mouse regions in rituximab.…”

Section: Introductionmentioning

confidence: 99%

A new anti-idiotype antibody capable of binding rituximab on the surface of lymphoma cells

Cragg

Bayne

Tutt

et al. 2004

Blood

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The chimeric anti-CD20 monoclonal antibody (mAb), rituximab, is an established part of the management of many nonHodgkin lymphomas. The in vivo action of rituximab remains elusive, and this partially reflects a lack of highly specific reagents to detect rituximab binding at the cell surface. Here we report a new high-affinity mAb (MB2A4) with fine specificity for the idiotype of rituximab. It is able to detect rituximab in vitro, in the presence of high levels of human immunoglobulin G (IgG), in the serum of patients receiving rituximab therapy, and, surprisingly, when rituximab is bound to CD20 on the cell surface. We propose that the anti-idiotype (Id) binds to rituximab molecules bound univalently at the cell surface, facilitated by the relatively high off-rate of IntroductionThe chimeric anti-CD20 monoclonal antibody (mAb), rituximab, has now been used in more than 300 000 patients and has become integrated into the treatment of many B-cell lymphomas. [1][2][3][4][5] The use of rituximab is likely to increase even further with the recent observations that it may be of clinical benefit to patients with autoimmune diseases. [5][6][7][8] Remarkably, given its widespread use, we still have a relatively poor understanding of the nature of rituximab binding to B cells and how this mAb actually mediates its therapeutic effects in vivo. 3,[9][10][11][12][13][14][15] There are currently few well-characterized, highly specific reagents to detect rituximab. Previous reagents have been polyclonal and directed either to the rituximab idiotype (Id) 16,17 or the remaining mouse regions in rituximab. 18 Clearly, these may suffer from batch variation, lack of specificity, and/or cross-reactivity to normal human immunoglobulin G (IgG). For this reason, we raised a highly specific mAb MB2A4 directed to the rituximab Id and have used this tool to probe the nature of rituximab binding to B-cell tumors. Study design Cell lines and antibodiesCells were obtained from the European collection of cell cultures (ECACC) and maintained in supplemented RPMI. mAbs and their fragments were produced using standard methods. 19 Generation of anti-Id mAbsAnti-Id mAbs were generated by immunizing Lou rats with purified rituximab F(abЈ) 2 fragments and fusing their splenocytes with NS-1 cells to generate hybridomas. The hybridomas were screened by enzyme-linked immunosorbent assay (ELISA) and assessed for binding to rituximabcoated plates. ELISA for rituximabTo detect rituximab in patient serum, MB2A4 was coated onto ELISA plates, blocked, and washed. Subsequently, appropriately diluted rituximab-containing samples were added to the plate for 90 minutes, washed, and incubated with anti-human Fc-horseradish peroxidase (Hu Fc-HRP) mAb (SB2H2) for 60 minutes, before further washing and addition of the ELISA substrate. Flow cytometry for the detection of cell-bound rituximabTo detect rituximab bound to the surface of CD20 ϩ cells, standard flow cytometry techniques were used. 20 Briefly, rituximab was coated to CD20 ϩ cells for 15 minutes at room te...

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Mechanism of action of rituximab

Cited by 187 publications

References 0 publications

The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors

The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors

Immunologic and Clinical Responses to Rituximab in a Child With Opsoclonus-Myoclonus Syndrome

A new anti-idiotype antibody capable of binding rituximab on the surface of lymphoma cells

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