Large-scale generation of mature monocyte-derived dendritic cells for clinical application in cell factories™

Berger, Thomas G.; Feuerstein, Bernadette; Strasser, Erwin; Hirsch, Ute; Schreiner, Doris; Schuler, Gerold; Schuler‐Thurner, Beatrice

doi:10.1016/s0022-1759(02)00189-8

Cited by 119 publications

(104 citation statements)

References 19 publications

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“…[35][36][37][38] Dendritic cell vaccine Monocytes were enriched from leukapheresis products by plastic adherence of peripheral blood mononuclear cells or by counterflow centrifugation using Elutra-cell separator (Gambro BCT) and single-use, functionally sealed disposable Elutra sets, as described before. 39 Monocytes were cultured in the presence of IL-4 (500 U/mL), GM-CSF (800 U/mL) (both Cellgenix) and KLH (10 mg/mL, Calbiochem). DCs were matured with autologous monocyte-conditioned medium (30%, v/v) supplemented with prostaglandin E2 (10 mg/mL, Pharmacia & Upjohn) and 10 ng/mL TNF-a (Cellgenix) for 48 h. 40 This procedure gave rise to mature DCs meeting the release criteria.…”

Section: Treatment Schedulementioning

confidence: 99%

Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

et al. 2015

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Melanoma patients with regional metastatic disease are at high risk for recurrence and metastatic disease, despite radical lymph node dissection (RLND). We investigated the immunologic response and clinical outcome to adjuvant dendritic cell (DC) vaccination in melanoma patients with regional metastatic disease who underwent RLND with curative intent. In this retrospective study, 78 melanoma patients with regional lymph node metastasis who underwent RLND received autologous DCs loaded with gp100 and tyrosinase and were analyzed for functional tumor-specific T cell responses in skin-test infiltrating lymphocytes. The study shows that adjuvant DC vaccination in melanoma patients with regional lymph node metastasis is safe and induced functional tumor-specific T cell responses in 71% of the patients. The presence of functional tumor-specific T cells was correlated with a better 2-year overall survival (OS) rate. OS was significantly higher after adjuvant DC vaccination compared to 209 matched controls who underwent RLND without adjuvant DC vaccination, 63.6 mo vs. 31.0 mo (p D 0.018; hazard ratio 0.59; 95%CI 0.42-0.84). Five-year survival rate increased from 38% to 53% (p < 0.01). In summary, in melanoma patients with regional metastatic disease, who are at high risk for recurrence and metastatic disease after RLND, adjuvant DC vaccination is well tolerated. It induced functional tumor-specific immune responses in the majority of patients and these were related to clinical outcome. OS was significantly higher compared to matched controls. A randomized clinical trial is needed to prospectively validate the efficacy of DC vaccination in the adjuvant setting.

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Section: Treatment Schedulementioning

confidence: 99%

Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

et al. 2015

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“…Monocyte-derived DCs were generated essentially as previously described (32). In brief, monocyte-derived DCs were harvested after 5 to 7 days of culture in the presence of 200 ng/ml rhGM-CSF and 100 ng/ml rhIL-4 (Peprotech, England).…”

Section: Generation Of Monocyte-derived Dcs and Lmp2a Loadingmentioning

confidence: 99%

Potent Dendritic Cell Vaccine Loaded with Latent Membrane Protein 2A (LMP2A)

et al. 2008

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“…Monocyte-derived Imm-DCs generated from PBMCs (obtained with informed consent and the approval by our institutional review board) were cultured for 6 days in RPMI 1640 medium containing 1% heat-inactivated autologous serum, 1000 U/ml GM-CSF (PeproTech), and 500 U/ml IL-4 (Diaclone Research) (43). OK-DCs were generated by treating Imm-DCs with 0.1 KE/ml (0.1 KE equals of 0.01 mg of dried streptococci) OK-432 (Chugai Pharmaceutical) for 1 day and were then used for fusion.…”

Section: Generation Of Dcsmentioning

confidence: 99%

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

Koido

Hara

Homma

et al. 2007

The Journal of Immunology

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Dendritic cell (DC)/tumor cell fusion cells (FCs) can induce potent CTL responses. The therapeutic efficacy of a vaccine requires the improved immunogenicity of both DCs and tumor cells. The DCs stimulated with the TLR agonist penicillin-killed Streptococcus pyogenes (OK-432; OK-DCs) showed higher expression levels of MHC class I and II, CD80, CD86, CD83, IL-12, and heat shock proteins (HSPs) than did immature DCs. Moreover, heat-treated autologous tumor cells displayed a characteristic phenotype with increased expression of HSPs, carcinoembryonic Ag (CEA), MUC1, and MHC class I (HLA-A2 and/or A24). In this study, we have created four types of FC preparation by alternating fusion cell partners: 1) immature DCs fused with unheated tumor cells; 2) immature DCs fused with heat-treated tumor cells; 3) OK-DCs fused with unheated tumor cells; and 4) OK-DCs fused with heat-treated tumor cells. Although OK-DCs fused with unheated tumor cells efficiently enhanced CTL induction, OK-DCs fused with heat-treated tumor cells were most active, as demonstrated by: 1) up-regulation of multiple HSPs, MHC class I and II, CEA, CD80, CD86, CD83, and IL-12; 2) activation of CD4+ and CD8+ T cells able to produce IFN- γ at higher levels; 3) efficient induction of CTL activity specific for CEA or MUC1 or both against autologous tumor; and 4) superior abilities to induce CD107+IFN-γ+CD8+ T cells and CD154+ IFN-γ+CD4+ T cells. These results strongly suggest that synergism between OK-DCs and heat-treated tumor cells enhances the immunogenicity of FCs and provides a promising means of inducing therapeutic antitumor immunity.

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Large-scale generation of mature monocyte-derived dendritic cells for clinical application in cell factories™

Cited by 119 publications

References 19 publications

Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

Potent Dendritic Cell Vaccine Loaded with Latent Membrane Protein 2A (LMP2A)

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

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