Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical application

Thurner, Beatrice; Röder, Claudia; Dieckmann, Detlef; Heuer, Marion; Kruse, Monika; Glaser, Anke; Keikavoussi, Petra; Kämpgen, Eckhart; Bender, Armin; Schuler, Gerold

doi:10.1016/s0022-1759(98)00208-7

Cited by 453 publications

(342 citation statements)

References 31 publications

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“…Peripheral blood mononuclear cells were isolated by centrifugation on Ficoll -Plaque Plus gradients (Amersham, Uppsala, Sweden). The procedure was carried out according to Thurner et al (1999) with minor modifications.…”

Section: In Vitro Priming Of Human Ctlmentioning

confidence: 99%

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

et al. 2007

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D bÀ/À xb2 microglobulin (b2m) null mice transgenic for a chimeric HLA-A2.1/D b -b2m single chain (HHD mice) are an effective biological tool to evaluate the antitumour cytotoxic T-lymphocyte response of known major histocompatibility-restricted peptide tumour-associated antigens, and to screen for putative unknown novel peptides. We utilised HHD lymphocytes to identify immunodominant epitopes of colon carcinoma overexpressed genes. We screened with HHD-derived lymphocytes over 500 HLA-A2.1-restricted peptides derived from colon carcinoma overexpressed genes. This procedure culminated in the identification of seven immunogenic peptides, three of these were derived from the 'human 1-8D gene from interferon inducible gene' (1-8D). The 1-8D gene was shown to be overexpressed in fresh tumour samples. The three 1-8D peptides were both antigenic and immunogenic in the HHD mice. The peptides induce cytotoxic T lymphocytes that were able to kill a colon carcinoma cell line HCT/HHD, in vitro and retard its growth in vivo. One of the peptides shared by all the 1-8 gene family primed efficiently normal human cytotoxic T lymphocyte precursors. These results highlight the 1-8D gene and its homologues as putative immunodominant tumour-associated antigens of colon carcinoma.

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Section: In Vitro Priming Of Human Ctlmentioning

confidence: 99%

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

et al. 2007

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“…In the other patients, PBMC were obtained from leukapheresis, and kept frozen until use. For each vaccination, part of the PBMC was thawed, and adherent cells were differentiated to immature DC as described (Thurner et al, 1999). Immature DC were loaded with 30 -200 mg of tumour proteins per million DC, depending on the material available.…”

Section: Preparation Of Autologous DCmentioning

confidence: 99%

“…The median yield of DC from freshly isolated PBMC was 4.8 Â 10 6 per injection (range: 0.8 -13 Â 10 6 ; n ¼ 37), which was significantly (Mann -Whitney test: P ¼ 0.0007) less than the median yield of DC from leukapheresis PBMC (median 10, range: 3 -18 Â 10 6 ; n ¼ 22). The quality of the DC was controlled by the expression of HLA-DR, CD80, CD86 and CD83 ( Figure 1) (Thurner et al, 1999).…”

Section: Vaccines Preparation and Characterisationmentioning

confidence: 99%

Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study

Rutkowski¹,

Vleeschouwer²,

et al. 2004

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Patients with relapsed malignant glioma have a poor prognosis. We developed a strategy of vaccination using autologous mature dendritic cells loaded with autologous tumour homogenate. In total, 12 patients with a median age of 36 years (range: 11 -78) were treated. All had relapsing malignant glioma. After surgery, vaccines were given at weeks 1 and 3, and later every 4 weeks. A median of 5 (range: 2 -7) vaccines was given. There were no serious adverse events except in one patient with gross residual tumour prior to vaccination, who repetitively developed vaccine-related peritumoral oedema. Minor toxicities were recorded in four out of 12 patients. In six patients with postoperative residual tumour, vaccination induced one stable disease during 8 weeks, and one partial response. Two of six patients with complete resection are in CCR for 3 years. Tumour vaccination for patients with relapsed malignant glioma is feasible and likely beneficial for patients with minimal residual tumour burden.

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“…In all the experiments, the spontaneous release was o25% of maximal release. Thurner et al (1999), with minor modifications. Briefly, in vitro priming was performed over autologous dendritic cells (DC) that were prepared from monocytes by IL-4 and GM-CSF treatment and matured with an IL-1b, IL-6, TNF-a, and PGE 2 cocktail.…”

Section: Vaccinationmentioning

confidence: 99%

MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

et al. 2004

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Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among women. Our study is aimed to characterise tumour-associated antigen peptides of transitional cell carcinoma of the bladder (TCC). A DNA micro-arraybased differential display analysis of 10 000 genes was carried out, and MAGE-A8 gene expression was detected in the tumour, and not in the normal bladder. High occurrence of MAGE-A8 expression was observed in fresh tumour samples (17 out of 23) and TCC lines (four of eight). The MAGE-A8 protein sequence was screened for HLA-A2.1-binding motifs, six potential peptides were synthesised, and peptides binding to HLA-A2.1 were assured. Immunogenicity and antigenicity of the MAGE-A8 peptides were examined in the HHD system, murine class I MHC knockout mice, transgenic for HLA-A2.1. The MAGE-A8 peptide immunogenicity was examined in three modes of vaccination, delivered intranasally with cholera toxin, injected into the tail base with complete Freund's adjuvant (CFA), or presented directly as loaded onto cell surface HLA-A2.1 molecules. Two peptides, 8.1 and 8.3, induce CTL that kills the T24 TCC line in vitro, and prime human lymphocyte response of healthy donors. These results demonstrate the potential use of the MAGE-A8 peptides for specific immunotherapy of TCC.

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Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical application

Cited by 453 publications

References 31 publications

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study

MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

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