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Foran, James M.; Cunningham, David; Solal-Celigny, P.; Reyes, F.; Ghielmini, M.; Johnson, P. W. M.; Gisselbrecht, C.; Bradburn, Michael; Matthews, J.; Lister, T. A.

doi:10.1023/a:1008309405678

Cited by 41 publications

(6 citation statements)

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“…[18][19][20] RTX has been used in clinical trials in newly-diagnosed and relapsed or refractory MCL, with ORR of 37%. 21 At M. D. Anderson Cancer Center, our upfront therapy for MCL is R-HyperCVAD/R-Methotrexate-Cytarabine. Its ORR was 97%, CR 87% and 3-year progression-free and overall survival rates were 64 and 82%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

et al. 2007

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Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor clinical outcome. Although front therapy induces a high rate of complete remission (CR), relapse is inevitable and new regimens are much needed for relapsed MCL. The proteasome inhibitor bortezomib (BTZ) induces apoptosis and sensitizes MCL cells to chemotherapy in relapsed MCL, but CR rates are low, with a short duration of response and severe toxicity. Here we evaluated whether BTZ is additive or synergistic with cyclophosphamide (CTX) and rituximab (RTX). Increasing doses of BTZ with a fixed dose of RTX and CTX (BRC regimen) resulted in markedly synergistic growth inhibition of MCL cells. BRC significantly enhanced apoptosis in MCL cell lines and primary tumor cells compared with singleagent treatment. Furthermore, western blotting analysis indicated that BRC induces apoptosis earlier via activation and cleavage of caspases-8, -9 and -3, and poly (ADP-ribose) polymerase, than single-agent treatment. The pan-caspase inhibitor completely blocked apoptosis induced by BRC. In vivo studies showed that BRC eradicated subcutaneous tumors in MCL-bearing SCID mice and significantly prolonged the longterm event-free survival in 70% of the mice. Hence, our study demonstrates that cytoreductive chemotherapy with both BTZ and anti-CD20 antibody may offer a better therapeutic modality for relapsed MCL.

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Section: Discussionmentioning

confidence: 99%

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

et al. 2007

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“…These include improvement of patient outcomes when combined with chemotherapy and limited toxicity profiles, making mAbs ideal alternative options for heavily pretreated patients with relapsed/refractory disease [24]. Rituximab (Genentech Inc, San Francisco, CA), a chimeric anti-human CD20 mAb, has been widely utilized to treat MCL patients [25, 26]. As a single agent, rituximab has been tested in untreated as well as pretreated patients with RR of approximately 30% and a median response duration of 6 months [25, 27].…”

Section: Introductionmentioning

confidence: 99%

“…Rituximab (Genentech Inc, San Francisco, CA), a chimeric anti-human CD20 mAb, has been widely utilized to treat MCL patients [25, 26]. As a single agent, rituximab has been tested in untreated as well as pretreated patients with RR of approximately 30% and a median response duration of 6 months [25, 27]. In combination with anthracycline-based regimens, rituximab significantly improved RR and time to progression of MCL patients when compared to patients treated with chemotherapy alone [28].…”

Section: Introductionmentioning

confidence: 99%

Novel targeted therapies for mantle cell lymphoma

2012

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Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy characterized by short median survival despite intensive therapies. The clinical behavior of MCL most likely relates to the complex pathophysiology of the disease which includes its genetic hallmark, the chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1, alteration in the DNA damage response, and constitutive activation of key antiapoptotic pathways such as phosphatidyl-inositol 3-kinase (PI3K)/Akt and nuclear factor-kB (NF-kB). Together, these changes result in cell cycle dysregulation and give rise to profound genetic instability. Given this complex pathophysiology, the limited number of options for patients with relapsed/refractory MCL, and the difficulty in achieving long-lasting remissions with conventional approaches, it is essential to explore new treatment options targeting the pathophysiology of MCL. We have recently reported that milatuzumab, a fully humanized anti-CD74 monoclonal antibody (mAb), in combination with anti-CD20 mAbs has significant preclinical and clinical activity in MCL. Here we discuss these results, provide additional insights into milatuzumab-mediated MCL cell death, and report preliminary data on the activity of other targeted biologic agents including PCI-32765, CAL-101 and mammalian target of rapamycin (mTOR) inhibitors currently undergoing evaluation at our institution and others.

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“…Mantle cell lymphoma (MCL) is a distinct clinical subtype of B cell non-Hodgkin’s lymphoma (NHL) and accounts for approximately 5%–10% of all lymphoma cases. Current treatment is based on standard chemotherapy often combined with monoclonal antibody rituximab, followed by hematopoietic stem cell transplantation [ 1 - 3 ]. Although these treatment regimens can induce a high rate of remission, most patients ultimately relapse and cannot be cured [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40

Chen

Zurawski²,

Zurawski³

et al. 2015

J Hematol Oncol

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BackgroundMantle cell lymphoma (MCL) is a distinct clinical pathologic subtype of B cell non-Hodgkin’s lymphoma often associated with poor prognosis. New therapeutic approaches based on boosting anti-tumor immunity are needed. MCL is associated with overexpression of cyclin D1 thus rendering this molecule an interesting target for immunotherapy.MethodsWe show here a novel strategy for the development of recombinant vaccines carrying cyclin D1 cancer antigens that can be targeted to dendritic cells (DCs) via CD40.ResultsHealthy individuals and MCL patients have a broad repertoire of cyclin D1-specific CD4+ and CD8+ T cells. Cyclin D1-specific T cells secrete IFN-γ. DCs loaded with whole tumor cells or with selected peptides can elicit cyclin D1-specific CD8+ T cells that kill MCL tumor cells. We developed a recombinant vaccine based on targeting cyclin D1 antigen to human DCs via an anti-CD40 mAb. Targeting monocyte-derived human DCs in vitro with anti-CD40-cyclin D1 fusion protein expanded a broad repertoire of cyclin D1-specific CD4+ and CD8+ T cells.ConclusionsThis study demonstrated that cyclin D1 represents a good target for immunotherapy and targeting cyclin D1 to DCs provides a new strategy for mantle cell lymphoma vaccine.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0131-7) contains supplementary material, which is available to authorized users.

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Cited by 41 publications

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Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

Novel targeted therapies for mantle cell lymphoma

A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40

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