Rituximab therapy in malignant lymphoma

Coiffier, Bertrand

doi:10.1038/sj.onc.1210376

Cited by 207 publications

(140 citation statements)

References 86 publications

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“…As shown in Figure 4d, the size of the subcutaneous tumor constantly increased in vehicle/IgG-treated control mice, and importantly, neither HDAC inhibitor alone nor rituximab alone inhibited tumor growth, consistent with the general consensus that Burkitt lymphoma is untreatable by these drugs as monotherapy. 3,4,7 In contrast, tumor growth was significantly retarded when two agents were combined (Figure 4d and Supplementary Figure S6). These results strongly suggest that HDAC inhibitors can potentiate the effects of rituximab in vivo by enhancing the expression of CD20.…”

Section: Hdac Inhibitors Enhance the Cytotoxic Effect Of Rituximab Inmentioning

confidence: 95%

“…2 Since being approved for clinical use in 1997, rituximab has given great benefits to patients with B-cell lymphomas, and has changed the paradigm of the treatment of indolent lymphomas. 3,4 Recently, rituximab resistance has emerged as an important clinical issue. 5 Although several mechanisms are proposed, loss of CD20 expression is undoubtedly one of the most straightforward and frequent causes of both innate and acquired resistance to rituximab in B-cell malignancies.…”

Section: Introductionmentioning

confidence: 99%

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HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells

et al. 2010

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Anti-CD20 antibody rituximab is now essential for the treatment of CD20-positive B-cell lymphomas. Decreased expression of CD20 is one of the major mechanisms underlying both innate and acquired resistance to rituximab. In this study, we show that histone deacetylase (HDAC) inhibitors augment the cytotoxic activity of rituximab by enhancing the surface expression of CD20 antigen on lymphoma cells. HDAC inhibitors, valproic acid (VPA) and romidepsin, increased CD20 expression at protein and mRNA levels in B-cell lymphoma cell lines with relatively low CD20 expression levels. The VPA-mediated increase in CD20 expression occurred at 1 mM, which is clinically achievable and safe, but insufficient for inducing cell death. Chromatin immunoprecipitation assays revealed that HDAC inhibitors transactivated the CD20 gene through promoter hyperacetylation and Sp1 recruitment. HDAC inhibitors potentiated the activity of rituximab in complementdependent cytotoxic assays. In mouse lymphoma models, HDAC inhibitors enhanced CD20 expression along with histone hyperacetylation in transplanted cells, and acted synergistically with rituximab to retard their growth. The combination with HDAC inhibitors may serve as an effective strategy to overcome rituximab resistance in B-cell lymphomas.

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Section: Hdac Inhibitors Enhance the Cytotoxic Effect Of Rituximab Inmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells

et al. 2010

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“…A few examples are outlined: (1) targeting of specific cell signaling pathways such as the epidermal growth factor inhibitorscetuximab (Erbitux), a chimeric (mouse/human) monoclonal antibody (mAb), used in the treatment of colorectal cancer and head and neck carcinoma [52][53][54][55], trastuzumab (Herceptin), an anti-HER2 mAb, used against breast tumors and metastatic gastric cancer-expressing HER2 [56]; (2) interference with tumor angiogenesis-bevacizumab (Avastin), an anti-VEGF-A humanized mAb, used against colorectal, lung, breast, glioblastoma, kidney, and ovarian tumors [57,58]; (3) targeting of specific tumor antigens-rituximab (MabThera), an anti-CD20 mAb, used against non Hodgkin's lymphoma [59]. A growing number of targeted treatments have reached the clinical setting; some replacing the conventional systemic treatments and others are used in conjunction with them to allow application of lower doses of the later, more toxic, drugs.…”

Section: Targeted Therapy-targeting Cscs In Wtmentioning

confidence: 99%

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

2013

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Wilms' tumor (WT), a common renal pediatric solid tumor, serves as a model for a malignancy formed by renal precursor cells that have failed to differentiate properly. Here we review recent evidence showing that the tumors' heterogeneous cell population contains a small fraction of cancer stem cells (CSC) identified by two markers: Neural Cell Adhesion Molecule 1 (NCAM1) expression and Aldehyde dehydrogenase 1 (ALDH1) enzymatic activity. In vivo studies show these CSCs to both self-renew and differentiate to give rise to all tumor components. Similar to other malignancies, the identification of a specific CSC fraction has allowed the examination of a novel targeted therapy, aimed at eradicating the CSC population. The loss of CSCs abolishes the tumor's ability to sustain and propagate, hence, causing tumor degradation with minimal damage to normal tissue.

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“…Follicular lymphoma (FL) is the most common subtype of indolent lymphoma. Rituximab is now widely used either alone or in combination with multi-agent chemotherapy for the treatment of FL, either at diagnosis (6,7), at relapse (8-10), or for maintenance therapy (2,11,12). However, despite its well-established clinical efficacy, a subpopulation of patients does not initially respond to rituximab and most patients will relapse after rituximab therapy (13,14).…”

Section: Introductionmentioning

confidence: 99%

“…It is the current treatment of choice for a variety of lymphoproliferative disorders including low and high grade B-cell non-Hodgkin's lymphomas (NHL; refs [1][2][3][4][5]. Follicular lymphoma (FL) is the most common subtype of indolent lymphoma.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Studies on the Mechanism of Action and the Anti-Lymphoma Activity of the Novel Anti-CD20 Antibody GA101

Dalle

Reslan

Horts

et al. 2011

Molecular Cancer Therapeutics

115

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GA101 is a novel glycoengineered Type II CD20 monoclonal antibody. When compared with rituximab, it mediates less complement-dependent cytotoxicity (CDC). As expected for a Type II antibody, GA101 appears not to act through CDC and is more potent than the Type I antibody rituximab in inducing cell death via nonclassical induction of apoptosis cytotoxicity, with more direct cytotoxicity and more antibody-dependent cell-mediated cytotoxicity. We evaluated the antitumor activity of GA101 against the human-transformed follicular lymphoma RL model in vivo in severe combined immunodeficient mice (SCID) mice. GA101 induced stronger inhibition of tumor growth than rituximab. Combination of GA101 with cyclophosphamide in vivo confirmed the superiority of GA101 over rituximab. Neutralizing the complement system with cobra venom factor partially impaired the antitumor activity of rituximab, but had no impact on the efficacy of GA101. In vitro GA101 more potently induced cell death of RL cells than rituximab. The expression of a limited number of genes was found to be induced by both antibodies after exposure in vitro. Among these, early growth response 1 and activation transcription factor 3 were confirmed to be increased at the protein level, suggesting a possible role of these proteins in the apoptotic signalling of anti-CD20 antibodies. These data imply that GA101 is superior to rituximab not only as a single agent, but also in combination with chemotherapy. These data suggest the presence of novel signalization pathways activated after exposure to anti-CD20 antibodies.

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Rituximab therapy in malignant lymphoma

Cited by 207 publications

References 86 publications

HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells

HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

Preclinical Studies on the Mechanism of Action and the Anti-Lymphoma Activity of the Novel Anti-CD20 Antibody GA101

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