Retroviral interleukin-7 gene transfer into human dendritic cells enhances T cell activation

Westermann, Jörg; Aicher, Alexandra; Qin, Zhihai; Cayeux, S; Daemen, Kerstin; Blankenstein, T; Dörken, Bernd; Pezzutto, Antonio

doi:10.1038/sj.gt.3300568

Cited by 48 publications

(36 citation statements)

References 42 publications

(43 reference statements)

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“…Infection of DC with recombinant retroviruses requires proliferating cell populations and frequently multiple rounds of infection are employed for efficient transduction. 19,38 Such retrovirus-transduced DC might produce OVA protein in sufficient amounts to achieve high OVA concentrations in the vicinity of the cell to allow antigen uptake into the endosomal compartment. In our study postmitotic differentiated DC were employed that are effectively transduced by Ad/PEI/DNA transfer complexes, [14][15][16] yet the production Gene Therapy of OVA protein might be too low to yield sufficiently high OVA concentrations at the cell surface for efficient endocytic uptake.…”

Section: Discussionmentioning

confidence: 99%

MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

et al. 2001

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Dendritic cells (DC) present immunogenic epitopes of antigens in the context of MHC class I and class II molecules in association with costimulatory molecules, and efficiently activate both cytotoxic T cells and T helper cells. Gene modified DC expressing antigen encoding cDNA represent a particularly attractive approach for the immunotherapy of disease. We previously described a gene delivery system for DC based on receptor-mediated endocytosis of ligand/polyethylenimine (PEI) DNA transfer complexes that target cell surface receptors which are abundantly expressed on DC. Employing this gene delivery system, DC were generated that express chicken ovalbumin (OVA) cDNA as a model antigen and introduce antigen into the

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Section: Discussionmentioning

confidence: 99%

MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

et al. 2001

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“…DC are attractive targets of gene transfer since DC are easily accessable and since these cells seem to be sensitive to immunologic strategies. For further enhancement of the antigeneic presentation by DC various genes like the genes for interleukin-7 (Westermann et al, 1998), GM -CSF, interleukin-12, interferon-gamma and interferon-alpha (Tüting et al, 1998) have been transfected into DC. Up to 10% transfection efficiencies using electroporation for gene transfer into CD83 + mononuclear cell derived DC were reported.…”

Section: Transfection Into Dendritic Cellsmentioning

confidence: 99%

Generation of dendritic cell-based vaccines for cancer therapy

Reinhard¹,

Märten²,

Kiske³

et al. 2002

Br J Cancer

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Dendritic cells play a major role in the generation of immunity against tumour cells. They can be grown under various culture conditions, which influence the phenotypical and functional properties of dendritic cells and thereby the consecutive immune response mainly executed by T cells. Here we discuss various conditions, which are important during generation and administration of dendritic cells to elicit a tumouricidal T cell-based immune response.

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“…10 Briefly, 625 to 10 000 irradiated (30 Gy) DC were used as stimulator cells together with 10 5 autologous T cells as responder cells in RPMI 1640 containing 10% FCS as a source of foreign antigen in a 5-day standard 3 H-thymidine incorporation assay.…”

Section: Mixed Lymphocyte Reaction (Mlr)mentioning

confidence: 99%

“…10 Briefly, 1.0 ml viral supernatant was added to 1 ϫ 10 6 target cells in 1.0 ml medium. Twelve hours later, two of three of the media were exchanged.…”

Section: Retroviral Transduction Of Dendritic Cellsmentioning

confidence: 99%

Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia

Westermann

Kopp

Körner

et al. 2000

Bone Marrow Transplant

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Summary:In chronic myeloid leukemia (CML) ex vivo generated DC are characterized by constitutive expression of bcr/abl and possibly other yet undefined leukemia-associated antigens, since these DC share a common progeny with leukemic cells. Induction of anti-leukemic T cell responses has been described in vitro. For a phase I vaccination study, autologous bcr/abl؉ DC are generated under GMP conditions mainly from monocyte precursors in chronic phase CML patients. Lin Induction of T cell immunity against leukemic cells by dendritic cells (DC) has been demonstrated in vitro both in chronic myeloid leukemia (CML) and in acute myeloid leukemia (AML).1-3 Chimeric fusion proteins resulting from chromosomal translocations can be considered as ideal target molecules for cytotoxic T cell responses, since these molecules are restricted to the malignant cell clone. In CML Ͼ90% of the patients express the 210 kDa chimeric fusion proteins bcr2/abl2 or bcr3/abl2. Both fusion proteins possess abnormal tyrosine kinase activity and play a key role in the pathogenesis of the disease. Within the fusion region of the bcr3/abl2 protein, different peptides have been identified which bind to HLA-A2, -A3, -A11 and -B8. 3,5-7 Furthermore, several HLA class II binding peptides have been isolated from the bcr/abl fusion region. Since DC can be generated in vitro from bcr/abl-positive precursors -CD34 ϩ cells and monocytes -the resulting DC population is largely bcr/abl-positive. In chronic phase CML, cytotoxic anti-leukemic T cell responses can be elicited by these unmodified DC, 1,8 possibly by constitutive presentation of bcr/ablϪ or other yet unknown peptides.In our GMP laboratory, autologous unmodified DC are generated as vaccine in patients with chronic phase bcr/ablpositive CML. Materials and methods Generation of DC for clinical application from monocytes according to GMP criteriaDC were generated from patients with chronic phase bcr/ablϩ CML according to our study protocol which had been approved by the local ethics committee. Peripheral blood mononuclear cells (PBMC) were collected by standard leukapheresis using an AS 104 cell separator (Fresenius, Bad Homburg, Germany). PBMC were further enriched by density gradient centrifugation on Lymphoprep (Life Technologies, Karlsruhe, Germany) and then stored on liquid nitrogen using RPMI 1640 (BioWhittaker, Verviers, Belgium) with 42.5% Human Serum Albumin (HSA, Octapharm) and 10% DMSO (Sigma). Thawing of PBMC was performed by addition of HBSS w/o Caϩϩ/Mgϩϩ (BioWhittaker) containing 5% HSA. PBMC were washed twice and then exposed to plastic adherence for monocyte enrichment. Briefly, PBMC were seeded at a density of 1.4 ϫ 10 6

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Retroviral interleukin-7 gene transfer into human dendritic cells enhances T cell activation

Cited by 48 publications

References 42 publications

MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

Generation of dendritic cell-based vaccines for cancer therapy

Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia

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