Dendritic cell vaccination in human melanoma: relationships between clinical effects and vaccine parameters

Nakai, Noriaki; Hartmann, Gunther; Kishimoto, Saburo; Katoh, Norito

doi:10.1111/j.1755-148x.2010.00736.x

Cited by 44 publications

(39 citation statements)

References 83 publications

(318 reference statements)

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“…However, the killing induced by alt-2 DC either via CD8 The mechanisms responsible for this dichotomy between an Agspecific and an innate mediated tumor killing might be due to the following: 1) Competition of effector cells for target during the assay. Despite the 1:1 ratio used in the degranulation assay, it is possible that in donors with higher levels of HLA and/or KIR mismatching with the used target cells, the enhanced innate killing might lead to the lack of targets for the adaptive response (2). The different outcome might be also mediated by distinct processes during the DC priming.…”

Section: Discussionmentioning

confidence: 98%

“…Clinical trials in different tumor entities have revealed safety and tolerability of such treatment. However, despite a frequent vaccineinduced expansion of precursor cells in the blood and/or the induction of delayed-type hypersensitivity, the rate of objective clinical responses obtained in tumor patients is very limited (1,2). For this reason, an optimization of the protocol for vaccine DC production as well as their deep functional characterization is urgently needed to improve their clinical implementation.…”

mentioning

confidence: 99%

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Fast Dendritic Cells Stimulated with Alternative Maturation Mixtures Induce Polyfunctional and Long-Lasting Activation of Innate and Adaptive Effector Cells with Tumor-Killing Capabilities

Massa

Seliger

2013

The Journal of Immunology

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The clinical usage of dendritic cells (DC) for tumor immunotherapy still requires improvements. In this study, three alternative maturation mixtures were compared with the cytokine-based gold standard, and the overall interaction of the resulting DC with effector cells from the innate as well as the adaptive immunity was evaluated in healthy donors. Stimulation with the TLR-4 ligand monophosphoryl lipid A together with IFN-γ (alt-2 DC) resulted in DC with the highest levels of costimulatory molecule expression and IL-12p70/IL-10 ratio. Whereas all alternative DC were able to induce NK and γδ T cells to acquire cytotoxic properties and secrete type 1 and proinflammatory cytokines, after both short (20-h)- and long (5–8 d)-time coculture, secretion of IFN-γ by the innate populations was induced in response to alt-2 and alt-1 DC (TNF-α, IFN-α, IFN-γ, IL-1β, poly IC), but not to alt-3 DC (TNF-α, IFN-γ, IL-1β, CL097). Regarding CD8+ T cell–mediated Ag-specific immune responses, a heterogeneous pattern of responses was obtained among the healthy donors, suggesting rather a competition than a synergy among the different effector cells. Our data promote further evaluation of alt-2 fast DC for translatability into clinical immunotherapy trials, while also fostering the need to identify biomarkers for immune cell responsiveness and tumor susceptibility to be able to select for each patient the best possible DC-based therapy.

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Fast Dendritic Cells Stimulated with Alternative Maturation Mixtures Induce Polyfunctional and Long-Lasting Activation of Innate and Adaptive Effector Cells with Tumor-Killing Capabilities

Massa

Seliger

2013

The Journal of Immunology

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“…and matured ones (8,9). Importantly, a plethora of clinical trials have demonstrated that DC vaccines are safe and well tolerated by cancer patients (4)(5)(6).…”

Section: Discussionmentioning

confidence: 99%

“…Currently DC vaccination is widely applied world wide with clinical responses achieved in up to 54% of patients (4,5). Therefore DC immu notherapy should be individualized in order to select cancer patients who would most likely respond to this kind of treatment.…”

Section: Introductionmentioning

confidence: 99%

Expression of tolerogenic potential-representing markers on clinical-grade therapeutic dendritic cell-based cancer vaccines

Dobrovolskiene¹,

Strioga²,

Liudkevičienė³

et al. 2014

AML

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Background. Currently a particular interest is given to specific active cancer immunotherapy (therapeutic cancer vaccination) strategies such as treatment with specially “educated” autologous dendritic cells (DCs). The purpose of these vaccines is to enhance antitumor immune responses against the existing tumor. DC vaccines are composed of tumor antigen-loaded mature DCs, which are produced for each cancer patient individually. However, recent data indicate that there are at least two types of mature DCs – immunogenic, which activate antitumor immune responses, and tolerogenic, which suppress immune responses, thereby interfering with effector mechanisms of protective antitumor immunity. Hence, the aim of our study was to assess the expression of immunogenic and tolerogenic potential-representing markers on the surface of therapeutic DC vaccines generated using two different maturation approaches. Materials and methods. Two different DC maturation approaches were investigated: Cocktail 1, composed of lipopolysaccharide (200 ng/ mL) and interferon-γ (50 ng/mL), and Cocktail 2, composed of IL1β (10 ng/mL), IL-6 (10 ng/mL), TNF-α (10 ng/mL), PGE2 (1 μg/mL). Secretion of two basic cytokines – the immunostimulatory IL-12p70 and the immunosuppressive IL-10 – has also been investigated. Results. We show that a subset of immature DCs expressed tolerogenic markers. Importantly their expression profile considerably differed on mature DCs, depending on the maturation approach used. Conclusions. In particular, our results indicate that Cocktail 1 is superior to Cocktail 2 for the production of clinical-grade therapeutic cancer DC vaccines, both in terms of immunophenotypical attributes of DC tolerogenicity and their cytokine secretory profile.

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“…One of the major disadvantages of this therapeutic strategy appears to be an induction of immunotolerance (in the context of the tumor microenvironment) and of immu nosuppressive T reg cells (Beyer and Schultze, 2009). To date, DC treatment protocols have been seen to be ineffective against advanced melanoma (Nakai et al, 2010).…”

Section: Immune Cells Modulation and Immunotherapy In Melanomamentioning

confidence: 99%

Microenvironment and tumor progression of melanoma: New therapeutic prospectives

Botti

Cerrone

Scognamiglio

et al. 2012

Journal of Immunotoxicology

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Dendritic cell vaccination in human melanoma: relationships between clinical effects and vaccine parameters

Abstract: SummaryEleven years have passed since the start of the first trial of dendritic cell (DC) vaccination for melanoma.A review of 54 trials was performed to evaluate the relationship between clinical effects and vaccine para-

Cited by 44 publications

References 83 publications

Fast Dendritic Cells Stimulated with Alternative Maturation Mixtures Induce Polyfunctional and Long-Lasting Activation of Innate and Adaptive Effector Cells with Tumor-Killing Capabilities

Fast Dendritic Cells Stimulated with Alternative Maturation Mixtures Induce Polyfunctional and Long-Lasting Activation of Innate and Adaptive Effector Cells with Tumor-Killing Capabilities

Expression of tolerogenic potential-representing markers on clinical-grade therapeutic dendritic cell-based cancer vaccines

Microenvironment and tumor progression of melanoma: New therapeutic prospectives

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