DNA Vaccines pp 267-286 | Cite as

Controlled Plasmid Delivery and Gene Expression

Applications for Nucleic Acid-Based Vaccines
  • Russell J. Mumper
  • Harry C. LedeburJr.
  • Alain P. Rolland
  • Eric Tomlinson
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 29)


After the concept of genetic immunization was first demonstrated by Johnston’s group in 1992 (1), numerous studies have reported the potential prophylactic and therapeutic use of nucleic acid-based vaccines for combating various infectious diseases (2, 3, 4). Vaccines of this composition appear to be both efficacious in the short term, and able to elicit a prolonged anamnestic response capable of preventing or resolving infection when challenged at up to one year after vaccination (5). Nucleic acid-based vaccines elicit a broader immune response than do subunit vaccines, inducing both cellular and humoral responses that are reminiscent of attenuated and whole-killed viral vaccines. Further, nucleic acid-based vaccines can be prepared with relative ease of synthesis and production. Expression plasmids can be generated quickly once the antigen’s coding sequence is known and small- and large-scale purification methods are well established. Nucleic acid-based vaccines also avoid some of the safety concerns of conventional vaccines in that there is no chance of disease due to co-purification of contaminating virus or reversion of the attenuated strain in the patient. This is not to claim that the safety issues surrounding nucleic acid-based vaccines are minimal. The major theoretical concerns surrounding the safety of this technology include plasmid integration into the host genome, transformation of somatic or stem cells, and tolerability. However, there is no published evidence that administration of unformulated or ‘naked’ plasmid produces a severe short or long term deleterious effect (6).


Intramuscular Administration Cationic Lipid Plasmid Delivery Single Plasmid Nuclease Degradation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Tang, D., DeVit, M., and Johnston, S. A. (1992) Genetic immunization is a simple method for eliciting an immune response. Nature 356, 152–154.PubMedCrossRefGoogle Scholar
  2. 2.
    Liu, M. A., Hilleman, M. R., and Kurth, R., eds. (1995) DNA Vaccines: A New Era in Vaccinology, Vol. 772, New York Academy of Science, New York.Google Scholar
  3. 3.
    Ulmer, J. B., Sadoff, J. C., and Liu, M. A. (1996) DNA vaccines. Curr. Opin. Immunol. 8, 531–536.PubMedCrossRefGoogle Scholar
  4. 4.
    Levine, M. M., Woodrow, G. C., Kaper, J. B., and Cobon, G. S., eds. (1997) New Generation Vaccines. Marcel Dekker, Inc. New York.Google Scholar
  5. 5.
    Yankauckas, M. A., Morrow, J. E., Parker, S. E., Abai, A., Rhodes, G. H., Dwarki, V. J., and Gromhowski, S. H. (1993) Long-term anti-nucleoprotein cellular and humoral immunity is induced by intramuscular injection of plasmid DNA containing NP gene. DNA Cell. Biol. 12, 771–776.PubMedCrossRefGoogle Scholar
  6. 6.
    Parker, S. E., Vahlsing, H. L., Serfilippi, L. M., Franklin, C. L., Doh, S. G., Gromkowski, S. H., Lew, et al. (1995) Cancer gene therapy using plasmid DNA: safety evaluation in rodents and non-human primates. Hum. Gene Ther. 6, 575–590.PubMedCrossRefGoogle Scholar
  7. 7.
    Food and Drug Administration: Center for Biologics Evaluation and Research (1997) Draft: Points to consider on plasmid DNA vaccines for preventive infectious disease indications.Google Scholar
  8. 8.
    Ulmer, J. B., Deck, R. R., Dewitt, C. M., Donnelly, J. I., and Liu, M. A. (1996) Generation of MHC class I-restricted cytotoxic T lymphocytes by expression of a viral protein in muscle cells: antigen presentation by non-muscle cells. Immunology 89, 59–67.PubMedCrossRefGoogle Scholar
  9. 9.
    Corr, M., Lee, D. J., Carson, D. A., and Tighe, H. (1996) Gene vaccination with naked plasmid DNA: mechanism of CTL priming. J. Exp. Med. 184, 1555–1560.PubMedCrossRefGoogle Scholar
  10. 10.
    Huang, A. Y. C., Golumbek, P., Ahmadzadeh, M., Jaffee, E., Pardoll, D., and Levitsky, H. (1994) Role of bone marrow derived cells in presenting MHC class I-restricted tumor antigens. Science 264, 961–965.PubMedCrossRefGoogle Scholar
  11. 11.
    Doe, B., Selby, M., Barnett, S., Baenziger, J., and Walker, C. M. (1996) Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells. Proc. Natl. Acad. Sci. USA 93, 8578–8583.PubMedCrossRefGoogle Scholar
  12. 12.
    Torres, C. A. T., Iwasaki, A., Barber, B. H., and Robinson, H. L. (1997) Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations. J. Immunol. 158, 4529–4532.PubMedGoogle Scholar
  13. 13.
    Condon, C., Watkins, S. C., Celluzzi, C. M., Thompson, K., and Falo, Jr., L. D. (1996) DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2, 1122–1128.PubMedCrossRefGoogle Scholar
  14. 14.
    Winegar, R. A., Monforte, J. A., Suing, K. D., O’Loughlin, K. G., Rudd, C. J., and MacGregor, J. T. (1996) Determination of tissue distribution of an intramuscular plasmid vaccine using PCR and in situ DNA hybridization. Hum. Gene Ther. 7, 2185–2194.PubMedCrossRefGoogle Scholar
  15. 15.
    Steinman, R. M. (1991) The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271–296.PubMedCrossRefGoogle Scholar
  16. 16.
    Shen, Z., Reznikoff, G., Dranoff, G., and Rock, K. L. (1997) Cloned dendritic cells can present exogenous antigens on both class I and class II molecules. J. Immunol. 158, 2723–2730.PubMedGoogle Scholar
  17. 17.
    Levy, M. Y., Barron, L. G., Meyer, K. B., and Szoka, F. C. (1996). Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism. expression and secretion of gene products into blood. Gene Ther. 3, 201–211.PubMedGoogle Scholar
  18. 18.
    Manthorpe, M., Cornefert-Jensen, F., Hartikka, J., Felgner, J., Rundell, A., Margalith, M., and Dwarki, V. (1993). Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum. Gene Ther. 4, 419–431.PubMedCrossRefGoogle Scholar
  19. 19.
    Wolff, J. A., Dowty, M. E., Jiao, S., Repetto, G., et al. (1992). Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle. J. Cell. Sci. 103, 1249–1259.PubMedGoogle Scholar
  20. 20.
    Davis, H. L., Demeneix, B. A., Quantin, B., Coulombe, J., and Whalen, R. G. (1993) Plasmid DNA is superior to viral vectors for direct gene transfer into adult mouse skeletal muscle. Hum. Gene Ther. 4, 733–740.PubMedCrossRefGoogle Scholar
  21. 21.
    Mumper, R. J., Duguid, J. G., Anwer, K., Barron, M. K., Nitta, H., and Rolland, A. P. (1996) Polyvinyl derivatives as novel interactive polymers for controlled gene delivery to muscle. Pharm. Res. 13, 701–709.PubMedCrossRefGoogle Scholar
  22. 22.
    Mumper, R. J., and Rolland, A. P. (1998) Plasmid delivery to muscle: recent advances in polymer delivery systems. Adv. Drug. Del. Rev. 30, 151–172.CrossRefGoogle Scholar
  23. 23.
    Mumper, R. J., Wang, J., Klakamp, S. L., Nitta, H., Anwer, A., Tagliaferri, F., and Rolland, A. P. (1998) Protective interactive non-condensing (PINC) polymers for enhanced plasmid distribution and expression in rat skeletal muscle. J. Controlled Rel. 52, 191–203.CrossRefGoogle Scholar
  24. 24.
    Alila, H., Coleman, M., Nitta, H., French, M., Anwer, K., Liu, Q., et al. (1997) Expression of biologically active human insulin-like growth factor-I following intramuscular injection of a formulated plasmid in rats. Hum. Gene. Ther. 8, 1785–1790.PubMedCrossRefGoogle Scholar
  25. 25.
    Kabanov, A. V, and Kabanov, V. A. (1995) DNA complexes with polycations for the delivery of genetic material into cells. Bioconjug. Chem. 6, 7–20.PubMedCrossRefGoogle Scholar
  26. 26.
    Anwer, K., Earle, K., Shi, M., Wang, J., Mumper, R. J., Procotr, B., Jansa, K., Ledebur, H. C., Davis, S., Eaglstein, W., and Rolland, A. P. (1999) Synergistic effect of formulated plasid and needle-free injection for genetic vaccines. J. Pharm. Res., in press.Google Scholar
  27. 27.
    Wagner, E., Zenke, M., Cotten, M., Beug, H., and Birnstiel, M. L. (1990) Transferrin polycation conjugates as carriers for DNA uptake into cells. Proc. Natl. Acad. Sci. USA 87, 3410–3414.PubMedCrossRefGoogle Scholar
  28. 28.
    Gottschalk, S., Cristiano, R. J., Smith, L. C., and Woo S. L. C. (1993) Folate receptor mediated DNA delivery into tumor cells: protosomal disruption results in enhanced gene expression. Gene Ther. 1, 185–191.Google Scholar
  29. 29.
    Buschle, M., Cotten, M., Kirlappos, H., Mechtler, K., Schaffner, G., Zauner, W., et al. (1995) Receptor-mediated gene transfer into human T lymphocytes via binding of DNA/CD3 antibody particles to the CD3 T-cell receptor complex. Hum. Gene Ther. 6, 753–761.PubMedCrossRefGoogle Scholar
  30. 30.
    Wu, G. Y., Wilson, J. M., Shalaby, F., Grossman, M., Shafritz, D. A., and Wu, C. H. (1991) Receptor-mediated gene delivery in vivo. J. Biol. Chem. 266, 14,338–14,342.PubMedGoogle Scholar
  31. 31.
    Midoux, P., Mendes, C., Legrand, A., Raimond, J., Mayer, R., Monsigny, M., and Roche, A. C. (1995) Specific gene transfer mediated by lactosylated poly-L-lysine into hepatoma cells. Nucleic Acids Res. 21, 871–878.CrossRefGoogle Scholar
  32. 32.
    Erbacher, P., Roche, A. C., Monsigny, M., and Midoux, P. (1995) Glycosylated polylysine/DNA complexes: gene transfer efficiency in relation with the size and the sugar substitution level of glycosylated polylysines and with the plasmid size. Bioconjug. Chem. 6, 401–410.PubMedCrossRefGoogle Scholar
  33. 33.
    Erbacher, P., Bousser, M. T., Raimond, J., Monsigny, M., Midoux, P., and Roche, A. C. (1996) Gene transfer by DNA/glycosylated polylysine complexes into human blood monocyte-derived macrophages. Hum. Gene Ther. 7, 721–729.PubMedCrossRefGoogle Scholar
  34. 34.
    Ferkol, T., Perales, J. C., Mularo, F., and Hanson, R. W. (1996) Receptor-mediated gene transfer into macrophages. Proc. Natl. Acad. Sci. USA 93, 101–105.PubMedCrossRefGoogle Scholar
  35. 35.
    Buschle, M., Schmidt, W., Zauner, W., Mechtler, K., Trska, B., Kirlappos, H., and Birnstiel, M. L. (1997) Transloading of tumor antigen-derived peptides into antigen presentingcells. Proc. Natl. Acad. Sci. USA 1, 3256–3261.CrossRefGoogle Scholar
  36. 36.
    Gottschalk, S., Sparrow, J. T., Hauer, J., Mims, M. P., Leland, F. E., Woo, S. L. C., and Smith, L. C. (1996) A novel DNA-peptide complex for efficient gene transfer and expression in mammalian cells. Gene Ther. 3, 448–457.PubMedGoogle Scholar
  37. 37.
    Ledley, F. D. (1996) Pharmaceutical approach to somatic gene therapy. Pharm. Res. 13, 1595–1614.PubMedCrossRefGoogle Scholar
  38. 38.
    Rolland, A. P. (1996) Controllable gene therapy: recent advances in non-viral gene delivery, in Targeting of Drugs 5: Strategies for Oligonucleotide and Gene Delivery in Therapy (Gregoriadis, G. and McCormack, B., eds.), Plenum Press, New York, pp. 79–95.Google Scholar
  39. 39.
    Mitchell, W. M., Rosenbloom, S.T., and Gabriel, J. (1995) Induction of mucosal anti HIV antibodies by facilitated transfection of airway epithelium with lipospermine/DNA complexes. Immunotechnology 1, 211–219.PubMedCrossRefGoogle Scholar
  40. 40.
    Wilke, M., Fortunati, E., van den Broek, M., Hoogeveen, A. T., and Scholte, B. J. (1996) Efficacy of a peptide-based gene delivery system depends on mitotic activity. Gene Ther. 3, 1133–1142.PubMedGoogle Scholar
  41. 41.
    Zhou, X., Klibanov, A. L., and Huang, L. (1991) Lipophilic polylysines mediate efficient DNA transfection in mammalian cells. Biochim. Biophys. Acta 1065, 8–14.PubMedCrossRefGoogle Scholar
  42. 42.
    Barry, M. A., Dower, W. J., and Johnston, S. A. (1996) Toward cell-targeting gene therapy vectors: selection of cell-binding peptides from random peptide-presenting phage libraries. Nat. Med. 2, 299–305.PubMedCrossRefGoogle Scholar
  43. 43.
    Ross, G., Erickson, R., Knorr, D., Motulsky, A. G., Parkman, R., Samulski, J., Straus, S. E., et al. (1996) Gene therapy in the United States: a five-year status report. Hum. Gene Ther. 7, 1781–1790.PubMedCrossRefGoogle Scholar
  44. 44.
    Middleton, P. G., Caplen, N. J., Gao, X., Huang, L., Gaya, H., Geddes, D. M., and Alton, E. W. (1994) Nasal application of the cationic liposome DC-Chol∶DOPE does not alter ion transport, lung function or bacterial growth. Eur. Respir. J. 7, 442–445.PubMedCrossRefGoogle Scholar
  45. 45.
    Nabel, E. G., Yang, Z., Muller, D., Chang, A. E., Gao, X., Huang, L., Cho, K. J., and Nabel, G. J. (1994) Safety and toxicity of catheter gene delivery to the pulmonary vasculature in a patient with metastatic melanoma. Hum. Gene Ther. 5, 1089–1094.PubMedCrossRefGoogle Scholar
  46. 46.
    Nabel, G. J., Nabel, E. G., Yang, Z. Y., Fox, B. A., Plautz, G. E., Gao, X., et al. (1993) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc. Natl. Acad. Sci. USA 90, 11,307–11,311.PubMedCrossRefGoogle Scholar
  47. 47.
    Gould-Fogerite, S., Mazurkiewicz, J. E., Raska, K., Voelkerding, K., Lehman, J. M., and Mannino, R. J. (1989) Chimerasome-mediated gene transfer in vitro and in vivo. Gene 84, 429–438.PubMedCrossRefGoogle Scholar
  48. 48.
    Mannino, R. J., and Gould-Fogerite, S. (1997) Antigen cochleate preparations for oral and systemic vaccination, in New Generation Vaccines (Levine, M. M., Woodrow, G. C., Kaper, J. B., and Cobon, G. S., eds.), Marcel Dekker, Inc. New York, pp. 229–238.Google Scholar
  49. 49.
    Hara, T., Liu, F., Liu, D., and Huang, L. (1997) Emulsion formulations as a vector for gene delivery in vitro and in vivo. Adv. Drug Del. Rev. 24, 265–271.CrossRefGoogle Scholar
  50. 50.
    Liu, F. Yang, J., Huang, L., and Liu, D. (1996) Effect of non-ionic surfactants on the formation of DNA/emulsion complexes and emulsion-mediated gene transfer. Pharm. Res. 13, 1642–1646.PubMedCrossRefGoogle Scholar
  51. 51.
    Liu, F., Yang, J., Huang, L., and Liu, D. (1996) New cationic lipid formulations for gene transfer. Pharm. Res. 13, 1856–1860.PubMedCrossRefGoogle Scholar
  52. 52.
    Zhou, X. and Huang, L. (1992) Targeted delivery of DNA by liposomes and polymers. J. Controlled Rel. 19, 269–274.CrossRefGoogle Scholar
  53. 53.
    Wang, C.Y. and Huang, L. (1989) Highly efficient DNA delivery mediated by pH sensitiveimmunoliposomes. Biochem. 28, 9508–9514.CrossRefGoogle Scholar
  54. 54.
    Mack, K. D., Walzem, R., and Zeldis, J. B. (1994) Cationic lipid enhances in vitro receptor-mediated transfection. Am. J. Med. Sci. 307, 138–143.PubMedCrossRefGoogle Scholar
  55. 55.
    Hara, T., Aramaki, Y, Takada, S., Koike, K., and Tsuchiya, S. (1995) Receptor-mediated transfer of pSV2CAT DNA to mouse liver cells using asialofetuin-labeled liposomes. Gene Ther. 2, 784–788.PubMedGoogle Scholar
  56. 56.
    Koike, K., Hara, T., Aramaki, Y., Takada, S., and Tsuchiya, S. (1994) Receptor-mediated gene transfer into hepatic cells using asialoglycoprotein-labeled liposomes. Ann. NY Acad. Sci. 716, 331–333.PubMedCrossRefGoogle Scholar
  57. 57.
    Cheng, P. W. (1995) Receptor ligand-facilitated gene transfer: enhancement of liposome-mediated gene transfer and expression by transferrin. Hum. Gene Ther. 7, 275–282.CrossRefGoogle Scholar
  58. 58.
    Nandi, P. K., Legrand, A., and Nicolau, C. (1986) Biologically active, recombinant DNA in clathrin-coated vesicles isolated from rat livers after in vivo injection of liposome-encapsulated DNA. J. Biol. Chem. 261, 16,722–16,726.PubMedGoogle Scholar
  59. 59.
    Stahl, P. D. (1992) The mannose receptor and other macrophage lectins. Curr. Opin. Immunol. 4, 49–52.PubMedCrossRefGoogle Scholar
  60. 60.
    Muller, C. D. and Schuber, F. (1989) Neo-mannosylated liposomes: synthesis and interaction with mouse Kupffer cells and resident peritoneal macrophages. Biochim. Biophys. Acta 986, 97–105.PubMedCrossRefGoogle Scholar
  61. 61.
    Barratt, G., Tenu, J. P., Yapo, A., and Petit, J. F. (1986) Preparation and characterization of liposomes containing mannosylated phospholipid capable of targetting drugs to macrophages. Biochim. Biophys. Acta 862, 153–164.PubMedCrossRefGoogle Scholar
  62. 62.
    Barratt, G., Nolibe, D., Yapo, A., Petit, J. F., and Tenu, J. P. (1987) Use of mannosylated liposomes for in vivo targeting of a macrophage activator and control of artificial pulmonary metastases. Ann. Inst. Pasteur/Immunol. 138, 437–450.CrossRefGoogle Scholar
  63. 63.
    Roche, A. C., Bailly, P., and Monsigny, M. (1985) Macrophage activation by MDP bound to neoglycoproteins: metastasis eradication in mice. Invasion Metastasis 5, 218–232.PubMedGoogle Scholar
  64. 64.
    Baldeschwieler, J. D. (1985) Phospholipid vesicle targeting using synthetic glycolipid and other determinants. Ann. NY Acad. Sci. 446, 349–367.PubMedCrossRefGoogle Scholar
  65. 65.
    Velinova, M., Read, N., Kirby, C., and Gregoriadis, G. (1996) Morphological observations on the fate of liposomes in the regional lymph nodes after footpad injection into rats. Biochim. Biophys. Acta 1299, 207–215.PubMedGoogle Scholar
  66. 66.
    Gregoriadis, G., Saffie, R., and de Souza, J. B. (1997) Liposome-mediated DNA vaccination. FEBS Lett. 402, 107–110.PubMedCrossRefGoogle Scholar
  67. 67.
    Moghimi, S. M. and Rajabi-Siahboomi, R. (1996) Advanced colloid-based systems for efficient delivery of drugs and diagnostic agents to the lymphatic tissue. Prog. Biophys. Mol. Biol. 65, 221–249.PubMedCrossRefGoogle Scholar
  68. 68.
    Hawley, A.E., Illum, L., and Davis, S.S. (1997) Lymph nodes localization of biodegradable nanospheres surface modified with poloxamer and poloxamine block co-polymers. FEBS Lett. 400, 319–323.PubMedCrossRefGoogle Scholar
  69. 69.
    Papisov, M., and Weissleder, R. (1996) Drug delivery to lymphatic tissue. Crit. Rev. Ther. Drug Carrier Syst. 13, 57–84.PubMedGoogle Scholar
  70. 70.
    Moghimi, S. M., Hawley, A. E., Christy, N. M., Gray, T., Illum, L., and Davis, S. S. (1994) Surface engineered nanospheres with enhanced drainage into lymphatics and uptake by macrophages of the regional lymph nodes. FEBS Lett. 344, 25–30.PubMedCrossRefGoogle Scholar
  71. 71.
    Fortin, A. and Therien, H. M. (1993) Mechanism of liposome adjuvanticity: an in vivo approach. Immunobiology 188, 316–322.PubMedGoogle Scholar
  72. 72.
    Alving, C. R. (1997) Liposomes as adjuvants for vaccines, in New Generation Vaccines (Levine, M. M., Woodrow, G. C., Kaper, J. B., and Cobon, G. S., eds.), Marcel Dekker, New York, pp. 207–214.Google Scholar
  73. 73.
    Watanabe, A., Raz, E., Kohsaka, H., Tighe, H., Baird, S. M., Kipps, T. J., and Carson, D. A. (1993) Induction of antibodies to a k V region by gene immunization. J. Immunol. 151, 2871–2876.PubMedGoogle Scholar
  74. 74.
    Xiang, Z. and Ertl, H. C. J. (1995) Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2, 129–135.PubMedCrossRefGoogle Scholar
  75. 75.
    Conry, R. M., Widera, G., LoBuglio, A. F., Fuller, J. T., Moore, S. E., Barlow, D. L., Turner, J., Yang, N-S., and Curiel, D. T. (1996) Selected strategies to augment polynucleotide immunization. Gene Ther. 3, 67–74.PubMedGoogle Scholar
  76. 76.
    Tsuji, T., Hamajima, K., Fukushima, J., Xin, K. Q., Ishii, N., Aoki, I., et al. (1997) Enhancement of cell-mediated immunity against HIV-1 induced by coinoculation of plasmid-encoded HIV-1 antigen with plasmid expressing IL-12. J. Immunol. 158, 4008–4013.PubMedGoogle Scholar
  77. 77.
    Geissler, M., Gesien, A., Tokushige, K., and Wands, J. R. (1997) Enhancement of cellular and humoral immune responses to hepatitis C virus core protein using DNA-based vaccines augmented with cytokine-expressing plasmids. J. Immunol. 158, 1231–1237.PubMedGoogle Scholar
  78. 78.
    Kim, J. J., Bagarazzi, M. L., Trivedi, N., Hu, Y., Kazahaya, K., Wilson, D. M., et al. (1997) Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes. Nat. Biotechnol. 15, 641–646.PubMedCrossRefGoogle Scholar
  79. 79.
    Schwartz, R. J., DeMayo, F. J., and O’Malley, B. W. Myogenic Vector Systems. United States Patent Number 5,298,422.Google Scholar
  80. 80.
    Coleman, M. E., DeMayo, F. J., Yin, K. C., Lee, H. M., Geske, R., Montgomery, C., and Schwartz, R. J. (1995) Myogenic vector expression of insulin-like growth factor I stimulates muscle cell differentiation and myofiber hypertrophy in transgenic mice. J. Biol. Chem. 270, 12,109–12,116.PubMedCrossRefGoogle Scholar
  81. 81.
    Zhou, L. J. and Tedder, T. F. (1995) Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J. Immunol. 154, 3821–3835.PubMedGoogle Scholar
  82. 82.
    Steinman, R. M., Pack, M., and Inaba, K. (1997) Dendritic cells in the T-cell areas of lymphoid organs. Immunol. Rev. 156, 25–37PubMedCrossRefGoogle Scholar
  83. 83.
    Jackson, J. J. and Kaminski, A. (1995) Internal initiation of translation in eukaryotes: the picornavirus paradigm and beyond. RNA 1, 985–1000.PubMedGoogle Scholar
  84. 84.
    Witherell, G. W., Schultz-Witherell, C. A., and Wimmer, E. (1995) Cis-acting elements of the encephalomyocarditis virus internal ribosomal entry site. Virology 214, 660–663.PubMedCrossRefGoogle Scholar
  85. 85.
    Zitvogel, L., Tahara, H., Cai, Q., Storkus, W. J., Muller, G., Wolf, S. F., et al. (1994) Construction and characterization of retroviral vectors expressing biologically active human interleukin-12. Hum. Gene Ther. 5, 1493–1506.PubMedCrossRefGoogle Scholar
  86. 86.
    Bramson, J., Hitt, M., Gallichan, W. S., Rosenthal, K. L., Gauldie, J., and Graham, F. L. (1996) Construction of a double recombinant adenovirus vector expressing a heterodimeric cytokine: in vitro and in vivo production of biologically active interleukin-12. Hum. Gene Ther. 7, 333–342.PubMedCrossRefGoogle Scholar
  87. 87.
    Tahara, H., Zitvogel, L., Storkus, W. J., Zeh III, H. J., McKinney, T. G., Schreiber, R. D., et al. (1995) Effective eradication of established murine tumors with IL-12 gene therapy using a poylcistronic retroviral vector. J. Immunol. 154, 6466–6474.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2000

Authors and Affiliations

  • Russell J. Mumper
    • 1
  • Harry C. LedeburJr.
    • 1
  • Alain P. Rolland
    • 1
  • Eric Tomlinson
    • 1
  1. 1.Gene Medicine Inc.The Woodlands

Personalised recommendations