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Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Munster, Munster, Germany
Bone marrow-derived dendritic cells (BmDC) are potent APC and can
promote antitumor immunity in mice when pulsed with tumor Ag. This
study aimed to define the culture conditions and maturation stages of
BmDC that enable them to optimally function as APC in vivo. BmDC
cultured under various conditions (granulocyte-macrophage CSF (GM-CSF)
or GM-CSF plus IL-4 alone or in combination with Flt3 ligand, TNF-
,
LPS, or CD40 ligand (CD40L)) were analyzed morphologically,
phenotypically, and functionally and were tested for their ability to
promote prophylactic and/or therapeutic antitumor immunity. Each of the
culture conditions generated typical BmDC. Whereas cells cultured in
GM-CSF alone were functionally immature, cells incubated with CD40L or
LPS were mature BmDC, as evident by morphology, capacity to internalize
Ag, migration into regional lymph nodes, IL-12 secretion, and
alloantigen or peptide Ag presentation in vitro. The remaining cultures
exhibited intermediate dendritic cell maturation. The in vivo
Ag-presenting capacity of BmDC was compared with respect to induction
of both protective tumor immunity and immunotherapy of established
tumors, using the poorly immunogenic squamous cell carcinoma, KLN205.
In correspondence to their maturation stage, BmDC cultured in the
presence of CD40L exhibited the most potent immunostimulatory effects.
In general, although not entirely, the capacity of BmDC to induce an
antitumor immune response in vivo correlated to their degree of
maturation. The present data support the clinical use of mature, rather
than immature, tumor Ag-pulsed dendritic cells as cancer vaccines and
identifies CD40L as a potent stimulus to enhance their in vivo
Ag-presenting capacity.
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S. Liu, Y. Yu, M. Zhang, W. Wang, and X. Cao The Involvement of TNF-{{alpha}}-Related Apoptosis-Inducing Ligand in the Enhanced Cytotoxicity of IFN-{{beta}}-Stimulated Human Dendritic Cells to Tumor Cells J. Immunol., May 1, 2001; 166(9): 5407 - 5415. [Abstract] [Full Text] [PDF]
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K. A. Candido, K. Shimizu, J. C. McLaughlin, R. Kunkel, J. A. Fuller, B. G. Redman, E. K. Thomas, B. J. Nickoloff, and J. J. Mulé Local Administration of Dendritic Cells Inhibits Established Breast Tumor Growth: Implications for Apoptosis-inducing Agents Cancer Res., January 1, 2001; 61(1): 228 - 236. [Abstract] [Full Text]
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L. A. Lambert, G. R. Gibson, M. Maloney, B. Durell, R. J. Noelle, and R. J. Barth Jr. Intranodal Immunization with Tumor Lysate-pulsed Dendritic Cells Enhances Protective Antitumor Immunity Cancer Res., January 1, 2001; 61(2): 641 - 646. [Abstract] [Full Text]
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C. Brunner, J. Seiderer, A. Schlamp, M. Bidlingmaier, A. Eigler, W. Haimerl, H.-A. Lehr, A. M. Krieg, G. Hartmann, and S. Endres Enhanced Dendritic Cell Maturation by TNF-{alpha} or Cytidine-Phosphate-Guanosine DNA Drives T Cell Activation In Vitro and Therapeutic Anti-Tumor Immune Responses In Vivo J. Immunol., December 1, 2000; 165(11): 6278 - 6286. [Abstract] [Full Text] [PDF]
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S. Koido, M. Kashiwaba, D. Chen, S. Gendler, D. Kufe, and J. Gong Induction of Antitumor Immunity by Vaccination of Dendritic Cells Transfected with MUC1 RNA J. Immunol., November 15, 2000; 165(10): 5713 - 5719. [Abstract] [Full Text] [PDF]
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K. Brasel, T. De Smedt, J. L. Smith, and C. R. Maliszewski Generation of murine dendritic cells from flt3-ligand-supplemented bone marrow cultures Blood, November 1, 2000; 96(9): 3029 - 3039. [Abstract] [Full Text] [PDF]
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D. Haddad, J. Ramprakash, M. Sedegah, Y. Charoenvit, R. Baumgartner, S. Kumar, S. L. Hoffman, and W. R. Weiss Plasmid Vaccine Expressing Granulocyte-Macrophage Colony-Stimulating Factor Attracts Infiltrates Including Immature Dendritic Cells into Injected Muscles J. Immunol., October 1, 2000; 165(7): 3772 - 3781. [Abstract] [Full Text] [PDF]
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I. E. A. Flesch, D. Stober, R. Schirmbeck, and J. Reimann Monocyte inflammatory protein-1{alpha} facilitates priming of CD8+ T cell responses to exogenous viral antigen Int. Immunol., September 1, 2000; 12(9): 1365 - 1370. [Abstract] [Full Text] [PDF]
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A. Mehling, S. Grabbe, M. Voskort, T. Schwarz, T. A. Luger, and S. Beissert Mycophenolate Mofetil Impairs the Maturation and Function of Murine Dendritic Cells J. Immunol., September 1, 2000; 165(5): 2374 - 2381. [Abstract] [Full Text] [PDF]
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M. Bellone, D. Cantarella, P. Castiglioni, M. C. Crosti, A. Ronchetti, M. Moro, M. P. Garancini, G. Casorati, and P. Dellabona Relevance of the Tumor Antigen in the Validation of Three Vaccination Strategies for Melanoma J. Immunol., September 1, 2000; 165(5): 2651 - 2656. [Abstract] [Full Text] [PDF]
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 J. W. Hodge, A. N. Rad, D. W. Grosenbach, H. Sabzevari, A. G. Yafal, L. Gritz, and J. Schlom Enhanced Activation of T Cells by Dendritic Cells Engineered to Hyperexpress a Triad of Costimulatory Molecules J Natl Cancer Inst, August 2, 2000; 92(15): 1228 - 1239. [Abstract] [Full Text] [PDF]
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S. Vendetti, J.-G. Chai, J. Dyson, E. Simpson, G. Lombardi, and R. Lechler Anergic T Cells Inhibit the Antigen-Presenting Function of Dendritic Cells J. Immunol., August 1, 2000; 165(3): 1175 - 1181. [Abstract] [Full Text] [PDF]
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D. H. Schuurhuis, S. Laban, R. E.M. Toes, P. Ricciardi-Castagnoli, M. J. Kleijmeer, E. I.H. van der Voort, D. Rea, R. Offringa, H. J. Geuze, C. J.M. Melief, et al. Immature Dendritic Cells Acquire Cd8+Cytotoxic T Lymphocyte Priming Capacity upon Activation by T Helper Cell-Independent or-Dependent Stimuli J. Exp. Med., July 3, 2000; 192(1): 145 - 150. [Abstract] [Full Text] [PDF]
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T. K. Hoffmann, N. Meidenbauer, G. Dworacki, H. Kanaya, and T. L. Whiteside Generation of Tumor-specific T Lymphocytes by Cross-Priming with Human Dendritic Cells Ingesting Apoptotic Tumor Cells Cancer Res., July 1, 2000; 60(13): 3542 - 3549. [Abstract] [Full Text]
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T. Kikuchi, M. A. S. Moore, and R. G. Crystal Dendritic cells modified to express CD40 ligand elicit therapeutic immunity against preexisting murine tumors Blood, July 1, 2000; 96(1): 91 - 99. [Abstract] [Full Text] [PDF]
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C. Klein, H. Bueler, and R. C. Mulligan Comparative Analysis of Genetically Modified Dendritic Cells and Tumor Cells as Therapeutic Cancer Vaccines J. Exp. Med., May 15, 2000; 191(10): 1699 - 1708. [Abstract] [Full Text] [PDF]
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Y. Tada, A. Asahina, K. Nakamura, M. Tomura, H. Fujiwara, and K. Tamaki Granulocyte/Macrophage Colony-Stimulating Factor Inhibits IL-12 production of Mouse Langerhans Cells J. Immunol., May 15, 2000; 164(10): 5113 - 5119. [Abstract] [Full Text] [PDF]
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A. I. Chapoval, K. Tamada, and L. Chen In vitro growth inhibition of a broad spectrum of tumor cell lines by activated human dendritic cells Blood, April 1, 2000; 95(7): 2346 - 2351. [Abstract] [Full Text] [PDF]
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M. K. Song, S. W. Lee, Y. S. Suh, K. J. Lee, and Y. C. Sung Enhancement of Immunoglobulin G2a and Cytotoxic T-Lymphocyte Responses by a Booster Immunization with Recombinant Hepatitis C Virus E2 Protein in E2 DNA-Primed Mice J. Virol., March 15, 2000; 74(6): 2920 - 2925. [Abstract] [Full Text]
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S. M. Barratt-Boyes, M. I. Zimmer, L. A. Harshyne, E. M. Meyer, S. C. Watkins, S. Capuano III, M. Murphey-Corb, L. D. Falo Jr., and A. D. Donnenberg Maturation and Trafficking of Monocyte-Derived Dendritic Cells in Monkeys: Implications for Dendritic Cell-Based Vaccines J. Immunol., March 1, 2000; 164(5): 2487 - 2495. [Abstract] [Full Text] [PDF]
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S. Schnell, J. W. Young, A. N. Houghton, and M. Sadelain Retrovirally Transduced Mouse Dendritic Cells Require CD4+ T Cell Help to Elicit Antitumor Immunity: Implications for the Clinical Use of Dendritic Cells J. Immunol., February 1, 2000; 164(3): 1243 - 1250. [Abstract] [Full Text] [PDF]
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T. Fukao, S. Matsuda, and S. Koyasu Synergistic Effects of IL-4 and IL-18 on IL-12-Dependent IFN-{gamma} Production by Dendritic Cells J. Immunol., January 1, 2000; 164(1): 64 - 71. [Abstract] [Full Text] [PDF]
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S. Corinti, D. Medaglini, A. Cavani, M. Rescigno, G. Pozzi, P. Ricciardi-Castagnoli, and G. Girolomoni Human Dendritic Cells Very Efficiently Present a Heterologous Antigen Expressed on the Surface of Recombinant Gram-Positive Bacteria to CD4+ T Lymphocytes J. Immunol., September 15, 1999; 163(6): 3029 - 3036. [Abstract] [Full Text] [PDF]
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N. Kohrgruber, N. Halanek, M. Groger, D. Winter, K. Rappersberger, M. Schmitt-Egenolf, G. Stingl, and D. Maurer Survival, Maturation, and Function of CD11c- and CD11c+ Peripheral Blood Dendritic Cells Are Differentially Regulated by Cytokines J. Immunol., September 15, 1999; 163(6): 3250 - 3259. [Abstract] [Full Text] [PDF]
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C. Curiel-Lewandrowski, K. Mahnke, M. Labeur, B. Roters, W. Schmidt, R. D. Granstein, T. A. Luger, T. Schwarz, and S. Grabbe Transfection of Immature Murine Bone Marrow-Derived Dendritic Cells with the Granulocyte-Macrophage Colony-Stimulating Factor Gene Potently Enhances Their In Vivo Antigen-Presenting Capacity J. Immunol., July 1, 1999; 163(1): 174 - 183. [Abstract] [Full Text] [PDF]
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A. Melcher, S. Todryk, A. Bateman, H. Chong, N. R Lemoine, and R. G Vile Adoptive Transfer of Immature Dendritic Cells with Autologous or Allogeneic Tumor Cells Generates Systemic Antitumor Immunity Cancer Res., June 1, 1999; 59(12): 2802 - 2805. [Abstract] [Full Text] [PDF]
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B. W. Tillman, T. D. d. Gruijl, S. A. L.-d. Bakker, R. J. Scheper, H. M. Pinedo, T. J. Curiel, W. R. Gerritsen, and D. T. Curiel Maturation of Dendritic Cells Accompanies High-Efficiency Gene Transfer by a CD40-Targeted Adenoviral Vector J. Immunol., June 1, 1999; 162(11): 6378 - 6383. [Abstract] [Full Text] [PDF]
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