Rituximab: Mechanism of Action

Weiner, George J.

doi:10.1053/j.seminhematol.2010.01.011

Cited by 652 publications

(505 citation statements)

References 68 publications

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“…27 There is some evidence that antibody-dependent cellular cytotoxicity mediated by activation of natural-killer cells contributes to the clinical response to rituximab. 28 Investigators have postulated that intensive chemotherapy could compromise the effi cacy of rituximab by impairing immune cellular mechanisms. 5 However, the results of our study do not favour such a hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

et al. 2011

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“…The CD20 antibody Rituximab was the first antibody approved for the treatment of cancer and is meanwhile an essential component of most treatment strategies for B-cell lymphoma [3]. The success of Rituximab has been attributed to several characteristics including its ability to mediate Fc receptor-dependent effector mechanisms, such as complementand antibody-dependent cellular cytotoxicity (ADCC) of NK cells [4]. Despite the undisputed success of Rituximab in lymphoma therapy, some patients do not respond at all, others for a limited time only.…”

Section: Introductionmentioning

confidence: 99%

4‐1BB ligand modulates direct and Rituximab‐induced NK‐cell reactivity in chronic lymphocytic leukemia

et al. 2011

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NK cells play an important role in tumor immunosurveillance and largely contribute to the therapeutic success of anti-tumor antibodies like Rituximab. Here, we studied the role of the TNF family member 4-1BB ligand (4-1BBL) during the interaction of NK cells with chronic lymphocytic leukemia (CLL) cells. 4-1BBL was highly expressed on patient B-CLL cells in all 56 investigated cases. Signaling via 4-1BBL following interaction with 4-1BB, which was detected on NK cells of CLL patients but not healthy individuals, led to the release of immunoregulatory cytokines including TNF by CLL cells. CLL patient sera contained elevated levels of TNF and induced 4-1BB upregulation on NK cells, which in turn impaired direct and Rituximab-induced NK-cell reactivity against 4-1BBL-expressing targets. NK-cell reactivity was not only enhanced by blocking the interaction of NK cell-expressed 4-1BB with 4-1BBL expressed by CLL cells, but also by preventing 4-1BB upregulation on NK cells via neutralization of TNF in patient serum with Infliximab. Our data indicate that 4-1BBL mediates NK-cell immunosubversion in CLL, and thus might contribute to the reportedly compromised efficacy of Rituximab to induce NK-cell reactivity in the disease, and that TNF neutralization may serve to enhance the efficacy of Rituximab treatment in CLL.

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“…Several new antibodies with enhanced effector functions demonstrated that in vitro tests have been developed (e.g., Ofatumumab, Ocrelizumab, Veltuzumab, AME-133V, PRO131921 and GA101) [23], but to date their clinical performances are disappointed in direct comparison with rituximab [25], and whether such new antibodies will be clinically superior to rituximab therapy remains to be seen [26]. In recent years, requirements for developing new antibodies to provide effective therapies for those patients who are insensitive or develop resistance to rituximab are increasingly urgent [23].…”

Section: Background 419mentioning

confidence: 99%

Investigating the Molecular Specific Interactions on Cell Surface Using Atomic Force Microscopy

Liu

et al. 2015

Micro‐ and Nanomanipulation Tools

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Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries [1]. The new cancer cases will increase from 12.7 million in 2008 to 22.2 million by 2030, while the cancer-related deaths will increase from 7.6 million in 2008 to 13.2 million by 2030 [2]. Carcinogenesis and tumor progression are complex and progressive processes that are associated with numerous genetic and epigenetic alterations [3]. Our growing understanding of tumor biology and genomics paves the way to the development of new therapy approaches, and marked progress has been achieved in overcoming treatment resistance through precision medicine and immunotherapy [4]. However, because of the fact that the exact reason why a cell becomes cancerous is unknown (the only one cancer whose cause is clear is cervical cancer), the current cancer treatments cannot prevent the recurrence of cancers and the age-adjusted mortality rate for cancer is about the same in the twenty-first century as it was 50 years ago [5].Lymphomas, solid tumors of the immune system [6], account for 4%-5% of all cancers [7]. Hodgkin's lymphoma accounts for about 10% of all lymphomas and the remaining 90% are referred to as non-Hodgkin lymphoma (NHL) [6]. NHL can be divided into many subtypes according to the combination of morphology, immunophenotype, genetic, molecular, and clinical features of the tumors [8]. Approximately, 85% of NHL in adults arises from B cells [9], and the rest are T-cell origin [10]. Follicular lymphoma and diffuse large B-cell lymphoma are the two most common B-cell NHLs, comprising 60% of new B-cell NHL diagnoses each year in North America [11]. In 1997, US Food and Drug Administration (FDA) approved rituximab (an anti-CD20 monoclonal antibody (mAb)) for treating B-cell NHLs. CD20 is 297 amino acids long with a molecule weight of about 33 kDa [12]. The exact biological function of CD20 is currently unknown [13], partly because it has no known natural ligand and CD20 knockout mice display an almost normal phenotype [14]. Many of the functions of CD20 have been determined using artificial ligands (antibody) [15]. In vitro experiments proposed that CD20

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Rituximab: Mechanism of Action

Cited by 652 publications

References 68 publications

Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

4‐1BB ligand modulates direct and Rituximab‐induced NK‐cell reactivity in chronic lymphocytic leukemia

Investigating the Molecular Specific Interactions on Cell Surface Using Atomic Force Microscopy

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