Mechanism of Cytotoxicity Induced by Chimeric Mouse Human Monoclonal Antibody IDEC-C2B8 in CD20-Expressing Lymphoma Cell Lines

Flieger, Dimitri; Renoth, Sabine; Beier, Imke; Sauerbruch, Tilman; Schmidt‐Wolf, Ingo G.H.

doi:10.1006/cimm.2000.1693

Cited by 136 publications

(101 citation statements)

References 36 publications

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“…Flieger et al [32] have shown that rituximab alone induced apoptosis in Raji lymphoma cell lines at a concentration above 100 ng/ml. There is general agreement that hyper-cross-linking enhances the apoptotic effects of CD20 mAbs [33].…”

Section: Ao/eb Double Fluorescent Stainingmentioning

confidence: 99%

Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy

Liu

et al. 2011

Biochemical and Biophysical Research Communications

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Section: Ao/eb Double Fluorescent Stainingmentioning

confidence: 99%

Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy

Liu

et al. 2011

Biochemical and Biophysical Research Communications

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“…NHL histological subtypes at enrollment included 7 follicular lymphoma (4 grade I and 3 grade II), 4 diffuse large cell lymphoma, 2 small cell lymphocytic lymphoma, 1 extranodal marginal zone lymphoma, and 1 mantle cell lymphoma ( Table 1). The median number of prior therapies was 4 (range, [2][3][4][5][6][7][8][9][10][11][12][13][14]. Ten patients who participated in study NHL02 had been treated previously with a total of 16 prior courses of rituximab therapy, alone (n ϭ 13), with combination chemotherapy (n ϭ 2), or with chemotherapy and transplantation (n ϭ 1).…”

Section: Patient Characteristicsmentioning

confidence: 99%

Phase I Studies of Interleukin (IL)-2 and Rituximab in B-Cell Non-Hodgkin’s Lymphoma

Gluck

Hurst

Yuen

et al. 2004

Clinical Cancer Research

153

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Purpose: Expansion and activation of natural killer (NK) cells with interleukin-2 (IL-2) may enhance antibodydependent cellular cytotoxicity (ADCC), an important mechanism of rituximab activity. Two parallel Phase I studies evaluated combination therapy with rituximab and IL-2 in relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).Experimental Design: Thirty-four patients with advanced NHL received rituximab (375 mg/m 2 i.v. weekly, weeks 1-4) and escalating doses of s.c. IL-2 [2-7.5 MIU daily (n ‫؍‬ 19) or 4.5-14 million international units three times weekly (n ‫؍‬ 15), weeks 2-5]. Safety, tolerability, clinical responses, NK cell counts, and ADCC activity were evaluated.Results: Maximally tolerated doses (MTD) of IL-2 were 6 MIU daily and 14 million international units thrice weekly. The most common adverse events were fever, chills, and injection site reactions. Dose-limiting toxicities were fatigue and reversible liver enzyme test elevations. Of the 9 patients enrolled at the daily schedule MTD, 5 showed clinical response. On the thrice-weekly schedule at the MTD, 4 of 5 patients responded. Responders showed median time to progression of 14.9 and 16.1 months, respectively, for the two studies. For the same total weekly dose, thrice-weekly IL-2 administration induced greater increases in NK cell counts than daily dosing, and NK cells correlated with clinical response on the thrice-weekly regimen. ADCC activity was increased and maintained after IL-2 therapy in responding and stable disease patients.Conclusions: Addition of IL-2 to rituximab therapy is safe and, using thrice-weekly IL-2 dosing, results in NK cell expansion that correlates with response. This combination treatment regimen merits additional evaluation in a randomized clinical trial.

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“…Although rituximab has multiple mechanisms of action, antibody-dependent cell-mediated cytotoxicity (ADCC) is of particular importance. Neutralizing antibodies that prevent the Fc-FcR-g interaction abrogate the B-celldepleting and antilymphoma activity in vitro 13 and in vivo in murine models. [14][15][16] In clinical practice, FcgRIIIA polymorphism with a higher affinity for IgG1 is associated with a higher response rate.…”

Section: Introductionmentioning

confidence: 99%

Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies

Kohrt

Thielens

Marabelle

et al. 2014

Blood

251

186

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Mechanism of Cytotoxicity Induced by Chimeric Mouse Human Monoclonal Antibody IDEC-C2B8 in CD20-Expressing Lymphoma Cell Lines

Cited by 136 publications

References 36 publications

Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy

Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy

Phase I Studies of Interleukin (IL)-2 and Rituximab in B-Cell Non-Hodgkin’s Lymphoma

Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies

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