Retention of B-cell-specific monoclonal antibodies by human lymphoma cells

Press, Oliver W.; Howell-Clark, Janet; Anderson, Shelby; Bernstein, Ira M.

doi:10.1182/blood.v83.5.1390.bloodjournal8351390

Cited by 33 publications

(34 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It decreases substantially in early plasmablasts and is extinguished upon terminal differentiation into mature plasma cells. Owing to its high and relatively sustained expression on neoplastic and normal B cells, CD20 represents an ideal target for immunotherapy of an ever‐growing variety of B cell disorders, both malignant and nonmalignant (16, 17). Indeed, since its approval in 1997 for the treatment of non‐Hodgkin's lymphoma, the use of rituximab has expanded into additional malignant conditions as well as autoimmune diseases of proven or presumed B cell origin (18).…”

mentioning

confidence: 99%

B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose‐escalation trial of rituximab

Looney

Anolik

Campbell

et al. 2004

Arthritis & Rheumatism

715

482

View full text Add to dashboard Cite

Results. Rituximab was well tolerated in this patient population, with most experiencing no significant adverse effects. Only 3 serious adverse events, which were thought to be unrelated to rituximab administration, were noted. A majority of patients (11 of 17) had profound B cell depletion (to <5 CD19؉ B cells/ l). In these patients, the SLAM score was significantly improved at 2 and 3 months compared with baseline (P ‫؍‬ 0.0016 and P ‫؍‬ 0.0022, respectively, by paired t-test). This improvement persisted for 12 months, despite the absence of a significant change in anti-doublestranded DNA antibody and complement levels. Six patients developed human antichimeric antibodies (HACAs) at a level >100 ng/ml. These HACA titers were associated with African American ancestry, higher baseline SLAM scores, reduced B cell depletion, and lower levels of rituximab at 2 months after initial infusion.Conclusion. Rituximab therapy appears to be safe for the treatment of SLE and holds significant therapeutic promise, at least for the majority of patients experiencing profound B cell depletion. Based on these results, controlled trials of rituximab appear to be warranted.

show abstract

mentioning

confidence: 99%

B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose‐escalation trial of rituximab

Looney

Anolik

Campbell

et al. 2004

Arthritis & Rheumatism

715

482

View full text Add to dashboard Cite

show abstract

“…CD20 is first expressed in the early pre–B cell stage, and it remains present until terminal differentiation into plasma cells. The CD20 antigen represents an ideal target for immunotherapy of B cell lymphomas and, more recently, B cell–mediated autoimmune diseases due to its high and relatively sustained expression on malignant and normal B cells (4). Rituximab can effectively deplete B cells for several months and, as such, represents an effective treatment of B cell lymphoma (5).…”

mentioning

confidence: 99%

The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus

Anolik¹,

Campbell²,

Felgar³

et al. 2003

Arthritis & Rheumatism

405

252

View full text Add to dashboard Cite

Objective. Despite wide use of the anti-CD20 monoclonal antibody rituximab in the treatment of B cell lymphomas, the mechanism by which it causes B cell depletion remains a subject of controversy. As part of an ongoing phase I/II trial of rituximab in the treatment of systemic lupus erythematosus (SLE), we sought to determine whether the effectiveness of B cell depletion was influenced by polymorphisms of Fc receptors (FcR) on effector cells.Methods. During rituximab treatment of 12 SLE patients, B cell depletion was monitored as a function of the serum rituximab level and Fc␥RIIa and Fc␥RIIIa genotypes at baseline and at 1 month and 2 months after treatment. FcR genotypes were determined by polymerase chain reaction. Serum levels of rituximab were measured by enzyme-linked immunosorbent assay (ELISA). B lymphocyte percentages were assessed by flow cytometry.Results. B cell depletion was highly variable in this patient cohort, with B cell percentages at the 1-2-month posttreatment nadir ranging from undetectable (<0.1 cell/ l) to 16% (ϳ30 cells/ l) of the total peripheral blood lymphocytes. At 2 months posttreatment, B cell percentages were highly correlated with both the serum rituximab level and the Fc␥RIIIa genotype (R 2 ‫؍‬ 0.75, P ‫؍‬ 0.002). The Fc␥RIIIa genotype was a significant independent predictor of the efficacy of B cell depletion (P ‫؍‬ 0.019). Conclusion. These results highlight the potential variability of B cell depletion by rituximab in the treatment of autoimmune disease and indicate that Fc receptors are an important determinant of that variability. The findings further suggest the importance of antibody-dependent cell-mediated cytotoxicity and/or apoptosis induction via Fc␥RIIIa-expressing effector cells in the mechanism of B cell depletion by this widely used monoclonal antibody.Rituximab is a chimeric mouse-human monoclonal antibody against the B cell-specific antigen CD20, a cell surface protein believed to function in B cell cycle initiation and differentiation (1-3). CD20 is first expressed in the early pre-B cell stage, and it remains present until terminal differentiation into plasma cells. The CD20 antigen represents an ideal target for immunotherapy of B cell lymphomas and, more recently, B cell-mediated autoimmune diseases due to its high and relatively sustained expression on malignant and normal B cells (4). Rituximab can effectively deplete B cells for several months and, as such, represents an effective treatment of B cell lymphoma (5).Several potential mechanisms have been proposed as mediators of the effects of rituximab (6). Thus, in vitro studies have demonstrated that rituximab bound to CD20ϩ cells induces complement-dependent cytotoxicity (CDC) and, in the presence of effector cells, antibody-dependent cell-mediated cytotoxicity (ADCC) (5). Additionally, rituximab can induce B cell apoptosis when crosslinked by Fc␥ receptor (Fc␥R)-bearing cells (7). The relative importance of antibody-mediated apoptosis, CDC, and ADCC in the depletion of B cells by rituximab remains to be...

show abstract

“…The present paradigm for the development of these autoimmune diseases is that autoimmunity develops in four stages: 1 genetic predisposition, 2 initiation, 3 perpetuation and progression maybe associated with epitope spreading, and finally, when autoimmunity has developed past a certain threshold, 4 clinical disease 3 …”

Section: Introductionmentioning

confidence: 99%

“…Rituximab induces stringent and usually prolonged depletion of peripheral CD20‐positive cells. Because plasma cells are CD20‐negative, their number and function are not affected by RTX, thereby probably explaining why the antibody has little effect on serum total Ig titers 3 . Allergic reactions are a potential side‐effect of RTX as a result of antimouse antibody responses.…”

Section: Introductionmentioning

confidence: 99%

Clinical experience in using CD20 monoclonal antibody in treating severe systemic lupus erythematosus

Shahrir

Halim

Zainudin

et al. 2007

APLAR Journal of Rheumatology

View full text Add to dashboard Cite

Background and method:This clinical experience involved the treatment of resistant systemic lupus erythematosus (SLE) patients with CD20 monoclonal antibody. Five patients failed conventional therapy, two developed complications and one needed rituximab as an emergency measure. Four patients had lupus nephritis, three had autoimmune hemolytic anemia, two had immune thrombocytopenia and one had lupoid hepatitis. The patients were aged 14-49 years, (mean 28.63). Three were Malays, two Chinese, two Indian and one Turkish; six were females. Mean disease duration was 63.25 months and mean total rituximab dose received was 2812.50 mL.Results: Hemoglobin levels improved from 9.3 ± 5.7 to 13.1 ± 8.6 g/dL for two SLE patients with autoimmune hemolytic anemia after 34 weeks (P = 0.180). Platelet counts improved from 25 ± 17 to 198 ± 97 × 10 9 /high powered field from 0 to 10 weeks for three SLE patients with immune thrombocytopenia (P = 0.109). In the lupus nephritis patients on rituximab, serum albumin improved from 24.5 ± 23.2 to 37.5 ± 31.8 mmol/L (n = 3) from week 0 to week 17 (P = 0.100). Urine protein creatinine ratio improved from 0.55 ± 0.23 to 0.08 ± 0.03 g/mmol creatinine (P = 0.068) from week 0 to week 13. C3 and C4 improved from 90.8 ± 36.5 to 120.7 ± 37.9 (P = 0.07) and 21.6 ± 10.1-27.3 ± 16.2 mg/dL (P = 0.27), respectively, and Systemic Lupus Erythematosus Activity Disease Index was reduced from 17.9 ± 11.2 to 6.3 ± 6.8 (P = 0.375) after 8 weeks. Two patients developed drug reactions to rituximab. Conclusion:All of the patients responded to rituximab on top of their conventional therapy.

show abstract

Retention of B-cell-specific monoclonal antibodies by human lymphoma cells

Cited by 33 publications

References 0 publications

B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose‐escalation trial of rituximab

B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose‐escalation trial of rituximab

The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus

Clinical experience in using CD20 monoclonal antibody in treating severe systemic lupus erythematosus

Contact Info

Product

Resources

About