A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection

Jonuleit, Helmut; Giesecke‐Tuettenberg, Andrea; Tüting, Thomas; Thurner‐Schuler, Beatrice; Stuge, Tor B.; Paragnik, Lydia; Kandemir, Ayten; Lee, Peter P.; Schuler, Gerold; Knop, Jürgen; Enk, Alexander H.

doi:10.1002/ijc.1323

Cited by 338 publications

(250 citation statements)

References 30 publications

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“…27,35,36 Mature DCs are much more effective at activating naive T cells and inducing antigen-specific T-cell responses. 37,38 As for Va24 1 NKT cells, mature moDCs pulsed with aGalCer appear to have a better ability to induce Va24 1 NKT cell expansion than either immature moDCs or monocytes. 32 Here, we show that the expansion of Va24 1 NKT cells induced by naturally matured CD11c 1 DCs in IL-2/GM-CSF-cultured PBMCs was comparable to that induced by mature CD11c 1 moDCs stimulated additionally with LPS or cytokine cocktail.…”

Section: Discussionmentioning

confidence: 99%

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

Ishikawa¹,

Motohashi²,

Ishikawa³

et al. 2005

Intl Journal of Cancer

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Human invariant Vα24+ natural killer T (NKT) cells display potent antitumor activity upon stimulation. Activation of endogenous Vα24+ NKT cells would be one strategy for the treatment of cancer patients. For example, dendritic cells (DCs) loaded with a glycolipid NKT cell ligand, α‐galactosylceramide (αGalCer, KRN7000), are a possible tool for the activation and expansion of functional Vα24+ NKT cells in vivo. In this report, we demonstrate that the levels of expansion and the ability to produce IFN‐γ of Vα24+ NKT cells induced by αGalCer‐loaded whole PBMCs cultured with IL‐2 and GM‐CSF (IL‐2/GM‐CSF‐cultured PBMCs) were superior to those of cells induced by monocyte‐derived CD11c+ DCs (moDCs) developed with IL‐4 and GM‐CSF. Interestingly, CD11c+ cells in the IL‐2/GM‐CSF‐cultured PBMCs showed a mature phenotype without further stimulation and exerted potent stimulatory activity on Vα24+ NKT cells to enable them to produce IFN‐γ preferentially at an extent equivalent to mature moDCs induced by stimulation with LPS or a cytokine cocktail. Cocultivation with CD11c− cells in the IL‐2/GM‐CSF‐cultured PBMCs induced maturation of moDCs. In particular, CD11c−CD3+ T cells appeared to play important roles in DC maturation. In addition, TNF‐α was preferentially produced by CD11c−CD3+ T cells in IL‐2/GM‐CSF‐cultured PBMCs and was involved in the maturation of moDCs. Thus, the maturation of DCs induced by CD11c− T cells through TNF‐α production appears to result in the efficient expansion and activation of Vα24+ NKT cells to produce IFN‐γ preferentially. © 2005 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

Ishikawa¹,

Motohashi²,

Ishikawa³

et al. 2005

Intl Journal of Cancer

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“…Clearly, there is room for much improvement here. Since the function and the maturation stage of DCs can influence the vaccine results greatly (Jonuleit et al, 2001), a definite establishment of the DC phenotype that correlates with good clinical responses is needed. More recent trials in our institution concentrate on using Toll-like receptor 7 agonists (Imiquimod) applied to the skin to enhance the migration of DCs, and enhancement of the T-cell responses by infusion of cytokines, for example, IL-2 in combination with the DC vaccines.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients

Kyte

Kvalheim

et al. 2005

Br J Cancer

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Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 Â 10 7 transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre-and postvaccination peripheral blood samples. Serum prostatespecific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n ¼ 19, P ¼ 0.002, r ¼ 0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients.

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“…22 Indeed, there is preliminary evidence that mDC induce stronger T-cell responses than iDC in cancer patients. 23 However, some viruses commonly used as vectors for the delivery of Ag such as recombinant vaccinia -viruses (rVV) may inhibit the maturation of DC as a mechanism of immune evasion. 24 Thus, although rVV can induce strong immune responses, it remains unclear how these develop in the infected host.…”

Section: Introductionmentioning

confidence: 99%

Biased epitope selection by recombinant vaccinia-virus (rVV)-infected mature or immature dendritic cells

et al. 2003

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A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection

Cited by 338 publications

References 30 publications

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients

Biased epitope selection by recombinant vaccinia-virus (rVV)-infected mature or immature dendritic cells

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A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection

Cited by 338 publications

References 30 publications

Dendritic cell maturation by CD11c− T cells and Vα24+ natural killer T‐cell activation by α‐Galactosylceramide

Dendritic cell maturation by CD11c− T cells and Vα24+ natural killer T‐cell activation by α‐Galactosylceramide

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients

Biased epitope selection by recombinant vaccinia-virus (rVV)-infected mature or immature dendritic cells

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Product

Resources

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Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide