Dendritic Cells

Bell, Diana; Young, James W.; Banchereau, Jacques

doi:10.1016/s0065-2776(08)60023-1

Cited by 297 publications

(232 citation statements)

References 504 publications

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“…As a consequence, the use of DC is a promising approach in immunotherapy for cancer and infectious diseases. [1][2][3][4][5][6] Many different methods have been used to load DC with antigens before in vivo injection. Protein-or peptidepulsed DC have been shown to be potent inducers of antigen-specific antitumor responses both in a variety of experimental animal models and in cancer patients.…”

mentioning

confidence: 99%

Induction of Influenza Matrix Protein 1 and MelanA-specific T lymphocytes in vitro using mRNA-electroporated dendritic cells

et al. 2003

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Genetically modified dendritic cells (DC) constitute a promising approach in cancer immunotherapy. Viral gene delivery systems have been shown to be very efficient strategies, but safety concerns for their clinical use in immunotherapy remain an important issue. Recently, the technique of mRNA electroporation was described as a very efficient tool for the genetic modification of human monocyte-derived DC. Here, we show that transgene expression can be modulated by varying the amount of mRNA used for electroporation. We document that CD40 ligation leads to a significant production of IL-12 by the electroporated DC, although the level of IL-12 production is somewhat lower than for non-or mock-electroporated DC. Furthermore, we show that the electroporated DC can be frozen and thawed without loss of viability or function and that Influenza virus Matrix Protein 1 mRNA electroporated DC are capable of inducing a memory cytotoxic T lymphocyte response and are more potent in doing so than mRNA-pulsed DC. Similar results were obtained with MelanA/MART-1 mRNA electroporated DC. These results clearly indicate that mRNA-electroporated DC represent powerful candidates for use as tumor vaccines and could constitute an improvement compared with vaccines using peptide-pulsed DC.

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mentioning

confidence: 99%

Induction of Influenza Matrix Protein 1 and MelanA-specific T lymphocytes in vitro using mRNA-electroporated dendritic cells

et al. 2003

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“…There is ample evidence that DC are the primary instigators of naive T cell activation, and that they may determine the balance between tolerance and immunity. [1][2][3][4]41,42 The potential of these rare BM-derived APC to act as natural immunologic adjuvants has provided the basis for the evaluation of DC-based vaccines, including genetically engineered DC, for anticancer therapy. 33,34 On the other hand, DC appear to play important roles in central and peripheral tolerance.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] They exist as immature cells in non-lymphoid tissues, such as the skin 5 or airway mucosa, 6 where they capture and process foreign and self-Ag. DC that acquire Ag in the periphery migrate to secondary lymphoid tissue where they present antigenic peptides to T cells, express high levels of costimulatory molecules, and initiate immune responses.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of CTLA4Ig gene delivery and expression in vivo using retrovirally transduced myeloid dendritic cells that induce alloantigen-specific T cell anergy in vitro

et al. 2000

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Dendritic cells (DC) are highly specialised, bone marrow (BM)-derived antigen-presenting cells (APC) that initiate and regulate immune responses. They provide costimulatory signals (in particular, CD40 and the CD28 ligands CD80 and CD86) necessary for naive T cell activation. Functional expression of CD80 and CD86 is blocked by the fusion protein cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4Ig), that promotes tolerance induction in animals. Here, replicating mouse (B10; H2 b ) myeloid DC progenitors, were retrovirally transduced to express CTLA4Ig using the centrifugal enhancement method. Gene product was detected by immunocyto-or histochemistry. Maximal DC transduction efficiency was 62%. Compared with control, zeomycin-resistance gene (Zeo)-transduced DC, CTLA4Ig-expressing cells showed markedly impaired capacity to stimulate naive allogeneic (C3H; H2 k ) T cell proliferation and cytotoxic T lymphocyte (CTL) generation. Their ability to induce alloantigen-specific T cell hyporesponsiveness was

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“…The main APC type in this tissue is represented by Langerhans cells (LC), iDC that, upon antigen uptake and maturation traffick to lymph nodes, are able to activate both naive and memory T cells (Bell et al, 1999;Lanzavecchia and Sallusto, 2001) (Figures 1, 2).…”

Section: As Presenters Of Antigens Encapsulated In Sslmentioning

confidence: 99%

Encapsulation into sterically stabilised liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes

et al. 2004

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Tumour-associated antigens (TAA)-specific vaccination requires highly immunogenic reagents capable of inducing cytotoxic T cells (CTL). Soluble peptides are currently used in clinical applications despite an acknowledged poor immunogenicity. Encapsulation into liposomes has been suggested to improve the immunogenicity of discrete antigen formulations. We comparatively evaluated the capacity of HLA-A2.1 restricted Melan-A/MART-1 epitopes in soluble form (S) or following inclusion into sterically stabilised liposomes (SSL) to be recognised by specific CTL, to stimulate their proliferation and to induce them in healthy donors' peripheral blood mononuclear cells (PBMC), as well as in melanoma-derived tumour-infiltrating lymphocytes (TIL). HLA-A2.1 þ , Melan-A/ MART-1-NA-8 melanoma cells served as targets of specific CTL in 51Cr release assays upon pulsing by untreated or human plasmatreated soluble or SSL-encapsulated Melan-A/MART-1 27 -35 (M27 -35) or 26 -35 (M26 -35) epitopes. These reagents were also used to stimulate CTL proliferation, measured as 3H-thymidine incorporation, in the presence of immature dendritic cells (iDC), as antigen-presenting cells (APC). Induction of specific CTL upon stimulation with soluble or SSL-encapsulated peptides was attempted in healthy donors' PBMC or melanoma-derived TIL, and monitored by 51Cr release assays and tetramer staining. Na-8 cells pulsing with SSL M27 -35 resulted in a five-fold more effective killing by specific CTL as compared with equal amounts of S M27 -35. Encapsulation into SSL also provided a partial (50%) protection of M27 -35 from plasma hydrolysis. No specific advantages regarding M26 -35 were detectable in these assays. However, at low epitope concentrations (p100 ng ml À1 ), SSL M26 -35 was significantly more effective in inducing CTL proliferation than S M26 -35, in the presence of iDC, as APC. Preincubation with iDC for 6 h virtually abolished the capacity of S M26 -35 to stimulate specific CTL proliferation, but only partially affected that of SSL M26 -35. Most importantly, SSL M26 -35 was able to enhance the induction of specific CTL in healthy donors PBMC and in melanoma-derived TIL as compared to S M26 -35. Taken together, our data indicate that encapsulation of TAA epitopes into SSL results in effective immunogenic formulations suitable for clinical use in active specific tumour immunotherapy.

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Dendritic Cells

Cited by 297 publications

References 504 publications

Induction of Influenza Matrix Protein 1 and MelanA-specific T lymphocytes in vitro using mRNA-electroporated dendritic cells

Induction of Influenza Matrix Protein 1 and MelanA-specific T lymphocytes in vitro using mRNA-electroporated dendritic cells

Feasibility of CTLA4Ig gene delivery and expression in vivo using retrovirally transduced myeloid dendritic cells that induce alloantigen-specific T cell anergy in vitro

Encapsulation into sterically stabilised liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes

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