DC preparations for therapy

Rice, A.; Jones, Kathryn L.; Hart, Derek N.J.

doi:10.1080/14653240410005285

Cited by 12 publications

(5 citation statements)

References 38 publications

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“…Most clinical trials using DC for cancer immunotherapy have been using iMoDC or mature MoDC, as they are easy to generate in large numbers [43,44]. However, some trials have used PBDC with relatively good results compared with MoDC, suggesting that PBDC represent more physiologically normal APC than in vitro-generated MoDC [44 -48].…”

Section: Discussionmentioning

confidence: 99%

Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets

Dalgaard

Beckstrøm

Jahnsen

et al. 2005

Journal of Leukocyte Biology

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CD11c+ dendritic cells (DC) and plasmacytoid DC (PDC) are the two major DC subsets in human peripheral blood. For the purpose of immunotherapy with DC, it is important to investigate the phagocytosis of killed tumor cells by different DC subsets. Using immature monocyte-derived DC (iMoDC) as reference, we have compared the ability of CD11c+ DC and PDC to phagocytose apoptotic and necrotic K562 leukemia cells. Freshly isolated CD11c+ DC phagocytosed apoptotic and necrotic K562 cells, whereas PDC did not show any evidence of uptake of dead cells. Blocking studies showed that CD36 is importantly involved in uptake of apoptotic and necrotic material. CD91 and CD11c were also involved. In addition, we found that beta5 integrin was expressed on CD11c+ DC but not in its classical association with alphaV. Uptake of apoptotic K562 cells by CD11c+ DC was increased following incubation with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4, alone or in combination with transforming growth factor-beta1, to levels comparable with those observed for iMoDC. Phagocytosis of dead cellular material by the GM-CSF/IL-4-treated CD11c+ DC was largely restricted to a subset expressing low levels of human leukocyte antigen-DR and CD83. Thus, the relationship between phagocytosis of antigenic material and expression of maturation-related cell-surface molecules is similar for CD11c+ DC and MoDC. We conclude that CD11c+ DC in peripheral blood are precursor cells, which under the influence of cytokines, differentiate to cells with DC phenotype and function.

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Section: Discussionmentioning

confidence: 99%

Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets

Dalgaard

Beckstrøm

Jahnsen

et al. 2005

Journal of Leukocyte Biology

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“…Such strategies will represent a novel approach of individualized immunotherapy using in vitro modified DCs as a complement to conventional immunosuppressive therapy. The capability for clinical application of such an approach is further supported by ongoing trials utilizing DC vaccines for cancer immunotherapy [90] which have generally proven to be safe, with minimal side effects and effective in certain patients [91]. However, whether IDO would need to be delivered to the entire graft (as outlined above) or just to a certain population of tolerogenic APCs deserves further investigation.…”

Section: Ido Expression As a Key Mechanism Of Tolerogenic Dendritic Cmentioning

confidence: 94%

Implications of IFN-γ-Mediated Tryptophan Catabolism on Solid Organ Transplantation

Brandacher¹,

Margreiter²,

Fuchs

2007

CDM

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The Th1-type cytokine interferon-gamma (IFN-gamma) is known as one of the most versatile players of the immune system. In transplantation immunology IFN-gamma has been shown to have contradictory effects on allograft survival via effects on both, the immune system and on the graft itself. The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO), widely distributed in mammals, is induced preferentially by IFN-gamma. IDO degrades the essential amino acid tryptophan to form N-formyl kynurenine which is subsequently converted to niacin. Recently, it has been proposed that IFN-gamma-mediated activation of IDO is critically involved in the regulation of immune responses, to establish immune-tolerance in pregnant mice upon their fetuses, or to induce T-cell unresponsiveness. Proliferation of alloreactive T-cells is thereby arrested via local tryptophan deprivation and the accumulation of toxic tryptophan catabolites. Despite growing recognition of the molecular T-cell regulatory mechanisms, the physiologic role of IDO in solid organ transplantation, however, remains unclear. Available experimental data indicate that IDO is involved in the mechanism of spontaneous donor-specific tolerance of liver grafts, and that genetic manipulation by introduction of the IDO gene into allografts is associated with prolonged survival. Furthermore, antigen-presenting cells, such as dendritic cells, can increase their expression of IDO, thus regulating immune responses. Based on these findings, the concept that cells expressing IDO can inhibit T-cell responses and hence induce tolerance has emerged as a new paradigm in immunology. Here we review the current literature on IDO in the context of transplantation and outline its potential implication as a target for tolerance induction.

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“…Recent results in experimental models that have examined the impact of infusion of DCs conditioned to be regulatory (or ‘tolerogenic’) DCs have fueled this enthusiasm, suggesting that regulatory DCs can drive in vivo generation of regulatory T cells (Treg), thus promoting robust peripheral tolerance [8]. The potential for clinical application of this approach is supported by ongoing clinical trials utilizing DC vaccines for tumor immunotherapy [9], as well as the fact that regulatory DC therapy in transplantation could be used in (and perhaps benefit from) the setting of conventional immunosuppression. In this review, we discuss DC biology and recent developments in the generation of regulatory DCs, as well as the hurdles for their application in clinical transplantation.…”

Section: Introduction: Clinical Need Tolerance and Regulatory Dcsmentioning

confidence: 99%

Regulatory dendritic cell therapy in organ transplantation

et al. 2006

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Summary Dendritic cells (DCs) are uniquely well equipped antigen (Ag)‐presenting cells. Their classic function was thought to be that of potent initiators of innate and adaptive immunity to infectious organisms and other Ags (including transplanted organs). Evidence has emerged, however, that DCs have a central and crucial role in determining the fate of immune responses toward either immunity or tolerance. This dichotomous function of DCs, coupled with their remarkable plasticity, renders them attractive therapeutic targets for immune modulation. In transplantation, much recent work has focused on the ability of DCs to silence immune reactivity in an Ag‐specific manner in the hope of preventing rejection and diminishing reliance on potentially harmful immunosuppressive agents. Experimental strategies have included in vivo targeting of DCs, as well as ex vivo generation of regulatory (or tolerogenic) DCs with subsequent reinfusion (i.e. cell therapy). Different approaches to ‘program’ DC toward tolerogenic properties include genetic (transgene insertion), biologic (differential culture conditions, anti‐inflammatory cytokine exposure) and pharmacologic manipulation. Recent data suggest a promising role for pharmacologic treatment as a means of generating potent regulatory DCs and have further stimulated speculation regarding their potential clinical application. Herein, we discuss evidence that the potential of regulatory DC therapy is considerable and that there are compelling reasons to evaluate it in the setting of organ transplantation in the near future.

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DC preparations for therapy

Cited by 12 publications

References 38 publications

Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets

Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets

Implications of IFN-γ-Mediated Tryptophan Catabolism on Solid Organ Transplantation

Regulatory dendritic cell therapy in organ transplantation

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DC preparations for therapy

Cited by 12 publications

References 38 publications

Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets

Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets

Implications of IFN-&#947;-Mediated Tryptophan Catabolism on Solid Organ Transplantation

Regulatory dendritic cell therapy in organ transplantation

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Implications of IFN-γ-Mediated Tryptophan Catabolism on Solid Organ Transplantation