The effects of CpG ODN on CLL proliferation, apoptosis or phenotype could have an impact on its clinical utility

Blackwell, Sue; Weiner, George J.

doi:10.1038/sj.leu.2404870

Cited by 9 publications

(6 citation statements)

References 4 publications

(6 reference statements)

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“…CpG-ODNs stimulate B-cells (including CLL cells), macrophages and dendritic cells via Toll-Like Receptor 9 (TLR9). CpG-ODNs have been demonstrated to induce proliferation of CLL cells 48, 49 . Additionally, stimulation with CpG-ODNs leads to an induction of pro-survival cytokine production; specifically TNF-α and IL-6, and increases in surface activation molecules, such as CD40, CD80 and CD86 49 .…”

Section: Pre-clinical Modeling In Vitromentioning

confidence: 99%

Preclinical modeling of novel therapeutics in chronic lymphocytic leukemia: the tools of the trade

Herman

Wiestner

2016

Seminars in Oncology

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In the last decade our understanding of chronic lymphocytic leukemia (CLL) biology and pathogenesis has increased substantially. These insights have led to the development of several new agents with novel mechanisms of action prompting a change in therapeutic approaches from chemotherapy based treatments to targeted therapies. Multiple pre-clinical models for drug development in CLL are available; however, with the advent of these targeted agents, it is becoming clear that not all models and surrogate readouts of efficacy are appropriate for all drugs. In this review we discuss in vitro and in vivo pre-clinical models, with a particular focus on the benefits and possible pitfalls of different model systems in the evaluation of novel therapeutics for the treatment of CLL.

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Section: Pre-clinical Modeling In Vitromentioning

confidence: 99%

Preclinical modeling of novel therapeutics in chronic lymphocytic leukemia: the tools of the trade

Herman

Wiestner

2016

Seminars in Oncology

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“…CpGstimulated normal B cells exhibit enhanced proliferation, cytokine production and upregulation of co-stimulatory molecules, 9 whereas malignant B cells hardly proliferate, but still develop an immunogenic phenotype that is better recognizable by immune cells than that of unstimulated cells. [10][11][12] In a murine xenograft model, CpG administration decreased leukemic burden 13 and induced durable remission and ongoing immune-mediated protection against leukemic growth, 14 but these advantageous effects of CpG have thus far not been translated into patients.…”

Section: Introductionmentioning

confidence: 99%

Acute lymphoblastic leukemia cells treated with CpG oligodeoxynucleotides, IL-4 and CD40 ligand facilitate enhanced anti-leukemic CTL responses

et al. 2011

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Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although the majority of patients initially respond to upfront chemotherapy, relapses with poor prognosis occur in approximately 20% of cases. Thus, novel therapeutic strategies are required to improve long-term survival. B-cell precursor (BCP)-ALL cells express low levels of immunogenic molecules and, therefore, are poorly recognized by the immune system. In the present study, we investigated the effect of various combinations of potent B-cell stimulators including CpG, Interleukin (IL)-2 family cytokines and CD40 ligand (CD40L) on the immunogenicity of primary BCP-ALL cells and a series of BCP-ALL cell lines. The combination of CpG, IL-4 and CD40L was identified as most effective to enhance expression of immunogenic molecules on BCP-ALL cells, resulting in an increased capacity to induce both allogeneic and autologous cytotoxic T lymphocytes (CTL). Importantly, such CTL exhibited significant anti-leukemic cytotoxicity not only towards treated, but also towards untreated BCP-ALL cells. Our results demonstrate that the combination of CpG with other B-cell stimulators is more efficient than CpG alone in generating immunogenic BCP-ALL cells and anti-leukemic CTL. Our results may stimulate the development of novel adoptive T cell transfer approaches for the management of BCP-ALL.

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“…Given the ability of CpG to induce CD25 expression, TLR9 ligands were also tested in vitro in combination with a specific anti-CD25 immunotoxin to treat CLL cells 81. Both TLR7 and TLR9 agonists have been studied for immunotherapy approaches in preclinical models of CLL in vitro ,73,82,83 and are currently under clinical investigation84–86 (see reference87 for a recent review on this topic).…”

Section: Tlr and Activation Of Leukemic Cellsmentioning

confidence: 99%

Toll-Like Receptors in Chronic Lymphocytic Leukemia

Muzio

Fonte²,

Caligaris-Cappio³

2012

Mediterr J Hematol Infect Dis

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Toll-like receptors belong to the pattern recognition receptors family present on a variety of immune cells including normal and malignant B-cells. They act as immediate molecular sentinels of innate immunity but also act as a molecular bridge between the innate and the adaptive immune response; distinct Toll-like receptors are able to bind specific pattern molecules of bacteria, viruses and autoantigens. In this review we will briefly introduce the Toll-like receptor family and their expression pattern, signaling and function in the B cell context; following we will summarize the published data on TLR in chronic lymphocytic leukemia, and we will discuss their emerging role in the modulation of leukemia pathobiology.

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The effects of CpG ODN on CLL proliferation, apoptosis or phenotype could have an impact on its clinical utility

Cited by 9 publications

References 4 publications

Preclinical modeling of novel therapeutics in chronic lymphocytic leukemia: the tools of the trade

Preclinical modeling of novel therapeutics in chronic lymphocytic leukemia: the tools of the trade

Acute lymphoblastic leukemia cells treated with CpG oligodeoxynucleotides, IL-4 and CD40 ligand facilitate enhanced anti-leukemic CTL responses

Toll-Like Receptors in Chronic Lymphocytic Leukemia

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