Abstract
Dendritic cells (DCs) are “professional” antigen-presenting cells (APCs) that are uniquely capable of activating and instructing a naive immune system to mount a specific cellular and humoral response. Recognition of this crucial function makes the development of technologies for DC-based immuno-therapies a priority for the treatment of a wide variety of diseases. The most immediate impact of this emerging technology will be in the treatment of cancer and the development of third generation vaccines to protect against viral and intracellular pathogens. In addition to elicitation of immune responses, DCs also function to maintain tolerance to “self.” Once the biological basis for this important function is understood, future applications of DC-based immuotherapies may be developed to ameliorate autoimmune diseases or enhance acceptance of transplanted organs. The feasibility of “engineering” the function of DCs has been realized by recent advances in ex vivo methodologies that allow selective DC propagation, antigen loading, and genetic modification in vitro for subsequent therapeutic transfer into the host. Ultimately, the ability to genetically modify these cells will allow us to design DC-mediated interventions that will direct predictable control of either immune activation or tolerance in vivo.
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References
Zhong, L., Granelli-Piperno, A., Choi, Y., and Steinman, R. M. (1999) Recombinant adenovirus is an efficient and non-perturbing genetic vector for human dendritic cells. Eur. J. Immunol. 29, 964–972.
Brossart, P., Goldrath, A. W., Butz, E. A., Martin, S., and Bevan, M. J. (1997) Virusmediated delivery of antigenic epitopes into dendritic cells as a means to induce CTL. J. Immunol. 158, 3270–3276.
Wan, Y., Emtage, P., Foley, R., Carter, R., and Gauldie, J. (1999) Murine dendritic cells transduced with an adenoviral vector expressing a defined tumor antigen can over come anti-adenovirus neutralizing immunity and induce effective tumor regression Int. J. Oncol. 14, 771–776.
Kaplan, J. M., Yu, Q., Piraino, S. T., Pennington, S. E., Shankara, S., Woodworth, L. A., and Roberts, B. L. (1999) Induction of antitumor immunity with dendritic cells transduced with adenovirus vector-encoding endogenous tumor-associated antigens. J. Immunol. 163, 699–707.
Tillman, B. W., de Gruijl, T. D., Luykx-deBakker, S. A., Scheper, R. J., Pinedo, H. M., Curiel, T. J., et al. (1999) Maturation of dendritic cells accompanies high-efficiency gene transfer by a CD40-targeted adenoviral vector. J. Immunol. 162, 6378–6383.
Rea, D., Schagen, F. H. E., Hoeben, R. C., Mehtali, M., Havenga, M. J. E., Toes, R. E. M., et al. (1999) Adnoviruses activate human dendritic cells without polarizaiton toward a T-helper type 1-inducing subset. J. Virol. 73, 10245–10253.
Tillman, B. W., Hayes, T. L., DeGruijl, T. D., Douglas, J. T., and Curiel, D. T. (2000) Adenoviral vectors targeted to CD40 enhance the efficacy of dendritic cell-based vaccination against human papillomavirus 16-induced tumor cells in a murine model. Cancer Res. 60, 5456–5463.
Caux, C., Vanbervliet, B., Massacrier, C., Dezutter-Dambuyant, C., de Saint-Vis, B., Jacquet, C., et al. (1996) CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. J. Exp. Med. 184, 695–706.
Schuler, G., Lutz, M., Bender, A., Thurner, B., Roder, C., Young, J. W., and Romani N. (1999) A guide to the isolation and propogation of dendritic cells, in Dendritic Cells (Lotz, M. T., and Thomson, A. W., eds.), Academic Press, New York, NY, pp. 515–553.
Inaba, K., Swiggard, W. J., Steinman, R. M., Romani, N., and Schuler, G. (1998) Generation of dendritic cells from proliferating mouse bone marrow progenitors, Unit 3.7, in Current Protocols of Immunology (Coico, R., ed.), Wiley, New York pp. 7–15.
Munn, D.H., Sharma, M. D., Lee, J. R., et al. (2002) Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297, 1867–1870.
Ebe, A., Schleidegger, S., Strunk, D., and Stingl, G. (1994). Fetal skin-derived MHC class I+, MHC class II-dendritic cells stimulate MHC class I-restricted responses of unprimed CD8+ T cells. J. Immunol. 153, 2878–2889.
Xu, S., Ariizumi, K., Edelbaum, D., Bergstresser, P., and Takashima, R. (1995) Successive generation of antigen-presenting, dendritic cell lines from murine epidermis. J. Immunol. 154, 2697–2705.
Jacob T., Saitoh, A., and Udey, M. C. (1997) E-caderhin-mediated adhesion involving Langerhans cell-like dendritic cells expanded from murine fetal skin. J. Immunol. 159, 2693–2701.
Winzler, C., Roveere, P., Rescigno, M., Granucci, F., Penna, G., Adorini, L., et al. (1997) Maturation stages of mouse dendritic cells in growth factor dependent longterm cultures. J. Exp. Med. 185, 317–328.
Timares, L., Takashima A., and Johnston S. A. (1998) Quantitative analysis of the immunopotency of genetically transfected dendritic cells. Proc. Natl. Acad. Sci. USA 95, 13147–13152.
Lyakh, L. A., Koski, G. K., Young, H. A., Spence, S. E., Cohen, P. A., and Rice, N. R. (2002) Adenovirus type 5 vectors induce dendritic cell differentiation in human CD14(+) monocytes cultured under serum-free conditions. Blood 99, 600–608.
Morelli, A. E., Larregina, A. T., Ganster, R. W., Zahorchak, A. F., Plowey, J. M., Takayama, T., et al. (2000) Recombinant adenovirus induces maturation of dendritic cells via an NF-kappaB-dependent pathway. J. Virol. 74, 9617–9628.
Romani, N., Reider, D., Heuer, M., Ebner, S., Kampgen, E., Eibl, B., et al. (1996) Generation of mature dendritic cells from human blood-an improved method with special regard to clinical applicability. J. Immunol. Methods 196, 137–151.
Gallucci, S., Lolkema, M., and Matzinger, P. (1999) Natural adjuvants: endogenous activators of dendritic cells. Nat. Medicine 5, 1249–1255.
Alam, J. and Cook, J. (1990) Reporter genes: Application to the study of mammalian gene transcription. Anal. Biochem. 188, 245–354.
Ranieri, E., Herr, W., Gambotto, A., Olson, W., Rowe, D., Robbins, P. D., et al. (1999) Dendritic cells transduced with an adenovirus vector encoding Epstein-Barr virus latent membrane protein 2B: a new modality for vaccination. J. Virol. 73, 10416–10425.
Brand, K., Klocke, R., Possling, A., Paul, D., and Strauss, M. (1999) Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection. Gene Ther. 6, 1054–1063.
Krasnykh, V., Dmitriev, I., Mikheeva, G., Miller, C. R., Belousova, N., and Curiel, D. T. (1998) Characterization of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob. J. Virol. 72, 1844–1852.
Asada-Mikami, R., Heike, Y., Kanai, S., Azuma, M., Shirakawa, K., Takaue, Y., et al. (2001) Efficient gene transduction by RGD-fiber modified recombinant adenovirus into dendritic cells. Japan. J. Cancer Res. 92, 321–327.
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Timares, L., Douglas, J.T., Tillman, B.W., Krasnykh, V., Curiel, D.T. (2004). Adenovirus-Mediated Gene Delivery to Dendritic Cells. In: Heiser, W.C. (eds) Gene Delivery to Mammalian Cells. Methods in Molecular Biology™, vol 246. Humana Press. https://doi.org/10.1385/1-59259-650-9:139
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DOI: https://doi.org/10.1385/1-59259-650-9:139
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