IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma.

Maloney, DG; Grillo-López, Antonio J; Bodkin, David; White, Christine; Liles, TM; Royston, Ivor; Varns, C.; Rosenberg, J.; Levy, Ronald

doi:10.1200/jco.1997.15.10.3266

Cited by 577 publications

(340 citation statements)

References 18 publications

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“…After rituximab administration, B lymphocyte depletion in patients occurs rapidly (within days) in the peripheral blood (17). Animal studies have shown that depletion of B cells in lymphoid tissue is rapid and unlikely to continue beyond 2 weeks (16).…”

Section: Discussionmentioning

confidence: 99%

“…Selective B lymphocyte depletion has been made possible by the availability of the chimeric anti-CD20 monoclonal antibody rituximab (16)(17)(18)(19)(20)(21). CD20 is a B lymphocyte-restricted antigen that is expressed on B lymphocyte precursors and mature B lymphocytes.…”

mentioning

confidence: 99%

“…Rituximab has been proven to be very effective in depleting normal and malignant B lymphocytes in vivo. In humans, peripheral B cell depletion occurs within days, and studies in primates have shown that up to 70% of B cells in lymphoid organs are also rapidly cleared (16,17,21). In autoimmune diseases, rituximab has been used in many cases as monotherapy (10)(11)(12).…”

mentioning

confidence: 99%

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Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Cambridge¹,

Leandro²,

Edwards³

et al. 2003

Arthritis & Rheumatism

413

259

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Objective. To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA).Methods. B lymphocyte depletion was attained using combination therapy based on the monoclonal anti-CD20 antibody rituximab. Levels of a serologic indicator of inflammation, C-reactive protein (CRP), of antimicrobial antibodies, of autoantibodies including IgA-, IgM-, and IgG-class rheumatoid factors (RF), and of antibodies to cyclic citrullinated peptide (anti-CCP) were assayed.Results. The majority of patients showed a marked clinical improvement after treatment with rituximab, with benefit lasting up to 33 months. Levels of total serum immunoglobulins fell, although the mean values each remained within the normal range. Whereas the IgM-RF response paralleled the changes in total serum IgM levels, the levels of IgA-RF, IgG-RF, and IgG and anti-CCP antibodies decreased significantly more than did those of their corresponding total serum immunoglobulin classes. The kinetics for the reduction in CRP levels also paralleled the decreases in autoantibody levels. In contrast, levels of antimicrobial antibodies did not change significantly. B lymphocyte return occurred up to 21 months posttreatment. The time to relapse after B lymphocyte return was often long and unpredictable (range 0-17 months). Relapse was, however, closely correlated with rises in the level of at least one autoantibody. Increased autoantibody levels were rarely observed in the absence of clinical change.Conclusion. Following B lymphocyte depletion in patients with RA, a positive clinical response occurred in correlation with a significant drop in the levels of CRP and autoantibodies. Antibacterial antibody levels were relatively well maintained. B lymphocyte return preceded relapse in all patients. There was also a temporal relationship between clinical relapse and rises in autoantibody levels. Although these observations are consistent with a role for B lymphocytes in the pathogenesis of RA, the precise mechanisms involved remain unclear.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Cambridge¹,

Leandro²,

Edwards³

et al. 2003

Arthritis & Rheumatism

413

259

View full text Add to dashboard Cite

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“…Several Ab have been developed and some of them are currently used in the treatment of patients with hematological malignancies and solid tumors [9]. Rituximab is the most extensively studied chimeric Ab and has been used for the treatment of lowgrade/follicular non-Hodgkin's lymphomas as a single therapeutic agent with a success rate of about 50% [10]. This mouse-human chimeric Ab is directed against CD20 expressed on mature B lymphocytes and on 90% of B cell non-Hodgkin's lymphomas and contains the complement -fixing human IgG1 and j regions [11,12].…”

Section: Introductionmentioning

confidence: 99%

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

et al. 2005

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Expression of the complement-regulatory proteins (CRP) CD46, CD55 and CD59 represents a strategy used by tumor cells to evade complement-dependent cell cytoxicity stimulated by monoclonal antibodies. We have isolated two single-chain variable fragments (scFv) to CD55 and CD59 from a human phage-display library and from these scFv we have produced two miniantibodies (MB), MB-55 (against CD55) and MB-59 (against CD59), containing the human hinge-CH2-CH3 domains of IgG1. The specificity of the two MB for the corresponding CRP was assessed by ELISA using purified CD46, CD55 and CD59. MB-55 and MB-59 neutralized the inhibitory activity of CD55 and CD59, respectively, restoring the complement-mediated lysis of sheep and guinea pig erythrocytes that was otherwise inhibited by the two CRP. FACS analysis revealed binding of MB-55 and MB-59 to the lymphoma cell line Karpas 422. The two MB induced a two-fold increase in the complement-dependent killing of these cells stimulated by Rituximab, a chimeric anti-CD20 monoclonal antibody. Transfection of HEK293T cells with vectors encoding MB-55 or MB-59 markedly reduced the expression of CD55 and CD59. We conclude that the human antibodies MB-55 and MB-59 may represent a therapeutic tool to increase the complement-dependent killing activity of Rituximab in the treatment of non-Hodgkin's lymphoma.

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“…The therapeutic administration of such monoclonal antibodies as trastuzumab, cetuximab, and rituximab targeting various proteins on the tumor cell membrane has brought about a milestone in the treatment of certain malignant diseases [4,5]. Although of high therapeutic efficacy, the passive antibody administration suffers from some drawbacks including the need of frequent administration of the drug in varying, but usually rather short time intervals, the necessity for a prolonged duration of drug delivery and the impossibility of application in a prophylactic manner in high-risk patients.…”

Section: Introductionmentioning

confidence: 99%

A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study

Wiedermann¹,

Wiltschke²,

Jasińska³

et al. 2009

Breast Cancer Res Treat

102

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IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma.

Abstract: IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma. The 375-mg/m2 dose has been selected for a phase II trial in patients with relapsed low-grade or follicular B-cell lymphoma.

Cited by 577 publications

References 18 publications

Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study

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