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Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 623687, 12 pages
http://dx.doi.org/10.1155/2010/623687
Review Article

RNA Vaccines in Cancer Treatment

Department of Oncology and Hematology, University Hospital Bonn, 53111 Bonn, Germany

Received 23 December 2009; Accepted 22 March 2010

Academic Editor: Hanchun Yang

Copyright © 2010 Anita Bringmann et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. H. Pilch, J. B. de Kernion, D. G. Skinner et al., “Immunotherapy of cancer with “immune” RNA. A preliminary report,” The American Journal of Surgery, vol. 132, no. 5, pp. 631–637, 1976. View at Publisher · View at Google Scholar
  2. Y. H. Pilch, K. P. Ramming, and J. B. DeKernion, “Preliminary studies of specific immunotherapy of cancer with immune RNA,” Cancer, vol. 40, no. 5, pp. 2747–2757, 1977. View at Google Scholar · View at Scopus
  3. G. Steele Jr., B. S. Wang, J. Richie et al., “In vivo effect and parallel in vitro lymphocyte-mediated tumor cytolysis after phase I xenogeneic immune RNA treatment of patients with widespread melanoma or metastatic renal cell carcinoma,” Cancer Research, vol. 40, no. 7, pp. 2377–2382, 1980. View at Google Scholar · View at Scopus
  4. I. Hoerr, R. Obst, H.-G. Rammensee, and G. Jung, “In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies,” European Journal of Immunology, vol. 30, no. 1, pp. 1–7, 2000. View at Publisher · View at Google Scholar · View at Scopus
  5. B. Weide, J.-P. Carralot, A. Reese et al., “Results of the first phase I/II clinical vaccination trial with direct injection of mRNA,” Journal of Immunotherapy, vol. 31, no. 2, pp. 180–188, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. P. van der Bruggen, C. Traversari, P. Chomez et al., “A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma,” Science, vol. 254, no. 5038, pp. 1643–1647, 1991. View at Google Scholar · View at Scopus
  7. P. G. Coulie, V. Brichard, A. Van Pel et al., “A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas,” The Journal of Experimental Medicine, vol. 180, no. 1, pp. 35–42, 1994. View at Publisher · View at Google Scholar · View at Scopus
  8. O. L. Caballero and Y.-T. Chen, “Cancer/testis (CT) antigens: potential targets for immunotherapy,” Cancer Science, vol. 100, no. 11, pp. 2014–2021, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. Y.-T. Chen, M. J. Scanlan, U. Sahin et al., “A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 5, pp. 1914–1918, 1997. View at Publisher · View at Google Scholar · View at Scopus
  10. T. Wolfel, M. Hauer, J. Schneider et al., “A p16(INK4a)-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma,” Science, vol. 269, no. 5228, pp. 1281–1284, 1995. View at Google Scholar · View at Scopus
  11. B. Fossum, T. Gedde-Dahl III, T. Hansen, J. A. Eriksen, E. Thorsby, and G. Gaudernack, “Overlapping epitopes encompassing a point mutation (12GlyArg) in p21 ras can be recognized by HLA-DR, -DP and -DQ restricted T cells,” European Journal of Immunology, vol. 23, no. 10, pp. 2687–2691, 1993. View at Google Scholar · View at Scopus
  12. S. Mandruzzato, F. Brasseur, G. Andry, T. Boon, and P. Van der Bruggen, “A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma,” The Journal of Experimental Medicine, vol. 186, no. 5, pp. 785–793, 1997. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Markowitz, J. Wang, L. Myeroff et al., “Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability,” Science, vol. 268, no. 5215, pp. 1336–1338, 1995. View at Google Scholar · View at Scopus
  14. R. Parsons, L. L. Myeroff, B. Liu et al., “Microsatellite instability and mutations of the transforming growth factor β type II receptor gene in colorectal cancer,” Cancer Research, vol. 55, no. 23, pp. 5548–5550, 1995. View at Google Scholar · View at Scopus
  15. I. Saeterdal, M. K. Gjertsen, P. Straten et al., “A TGF betaRII frameshift-mutation-derived CTL epitope recognised by HLA-A2-restricted CD8+ T cells,” Cancer Immunology, Immunotherapy, vol. 50, pp. 469–476, 2001. View at Google Scholar
  16. A. B. H. Bakker, M. W. J. Schreurs, A. J. de Boer et al., “Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes,” The Journal of Experimental Medicine, vol. 179, no. 3, pp. 1005–1009, 1994. View at Google Scholar · View at Scopus
  17. V. Brichard, A. Van Pel, T. Wolfel et al., “The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas,” The Journal of Experimental Medicine, vol. 178, no. 2, pp. 489–495, 1993. View at Google Scholar · View at Scopus
  18. T. Wolfel, A. Van Pel, V. Brichard et al., “Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes,” European Journal of Immunology, vol. 24, no. 3, pp. 759–764, 1994. View at Google Scholar · View at Scopus
  19. C. Adida, C. Haioun, P. Gaulard et al., “Prognostic significance of survivin expression in diffuse large B-cell lymphomas,” Blood, vol. 96, no. 5, pp. 1921–1925, 2000. View at Google Scholar · View at Scopus
  20. D. Grossman, J. M. McNiff, F. Li, and D. C. Altieri, “Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma,” Journal of Investigative Dermatology, vol. 113, no. 6, pp. 1076–1081, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. S. M. Schmidt, K. Schag, M. R. Muller et al., “Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells,” Blood, vol. 102, no. 2, pp. 571–576, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. P. Brossart, A. Schneider, P. Dill et al., “The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes,” Cancer Research, vol. 61, no. 18, pp. 6846–6850, 2001. View at Google Scholar · View at Scopus
  23. A. Girling, J. Bartkova, J. Burchell, S. Gendler, C. Gillett, and J. Taylor-Paradimitriou, “A core protein epitope of the polymorphic epithelial mucin detected by the monoclonal antibody SM-3 is selectively exposed in a range of primary carcinomas,” International Journal of Cancer, vol. 43, no. 6, pp. 1072–1076, 1989. View at Google Scholar · View at Scopus
  24. S. K. Nair, D. Boczkowski, M. Morse, R. I. Cumming, H. K. Lyerly, and E. Gilboa, “Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells transfected with RNA,” Nature Biotechnology, vol. 16, no. 4, pp. 364–369, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. F. K. Rae, S.-A. Stephenson, D. L. Nicol, and J. A. Clements, “Novel association of a diverse range of genes with renal cell carcinoma as identified by differential display,” International Journal of Cancer, vol. 88, no. 5, pp. 726–732, 2000. View at Publisher · View at Google Scholar · View at Scopus
  26. S. M. Schmidt, K. Schag, M. R. Muller et al., “Induction of adipophilin-specific cytotoxic T lymphocytes using a novel HLA-A2-binding peptide that mediates tumor cell lysis,” Cancer Research, vol. 64, no. 3, pp. 1164–1170, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Yokoyama, F. Grunebach, S. M. Schmidt et al., “Matrilysin (MMP-7) is a novel broadly expressed tumor antigen recognized by antigen-specific T cells,” Clinical Cancer Research, vol. 14, no. 17, pp. 5503–5511, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. F. Grunebach, S. Erndt, M. Hantschel, A. Heine, and P. Brossart, “Generation of antigen-specific CTL responses using RGS1 mRNA transfected dendritic cells,” Cancer Immunology, Immunotherapy, vol. 57, no. 10, pp. 1483–1491, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. C. N. Boss, F. Grunebach, K. Brauer et al., “Identification and characterization of T-cell epitopes deduced from RGS5, a novel broadly expressed tumor antigen,” Clinical Cancer Research, vol. 13, no. 11, pp. 3347–3355, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. Y. Oka, O. A. Elisseeva, A. Tsuboi et al., “Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms' tumor gene (WT1) product,” Immunogenetics, vol. 51, no. 2, pp. 99–107, 2000. View at Google Scholar · View at Scopus
  31. J. Molldrem, S. Dermime, K. Parker et al., “Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells,” Blood, vol. 88, no. 7, pp. 2450–2457, 1996. View at Google Scholar · View at Scopus
  32. J. J. Molldrem, E. Clave, Y. Z. Jiang et al., “Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units,” Blood, vol. 90, no. 7, pp. 2529–2534, 1997. View at Google Scholar · View at Scopus
  33. J. Greiner, M. Ringhoffer, M. Taniguchi et al., “Receptor for hyaluronan acid-mediated motility (RHAMM) is a new immunogenic leukemia-associated antigen in acute and chronic myeloid leukemia,” Experimental Hematology, vol. 30, no. 9, pp. 1029–1035, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. S. M. Schmidt, T. Konig, A. Bringmann et al., “Characterization of BAX inhibitor-1 as a novel leukemia-associated antigen,” Leukemia, vol. 23, no. 10, pp. 1818–1824, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. K. Inaba, S. Turley, T. Iyoda et al., “The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli,” The Journal of Experimental Medicine, vol. 191, no. 6, pp. 927–936, 2000. View at Publisher · View at Google Scholar · View at Scopus
  36. K. Inaba, M. Witmer-Pack, M. Inaba et al., “The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro,” The Journal of Experimental Medicine, vol. 180, no. 5, pp. 1849–1860, 1994. View at Publisher · View at Google Scholar · View at Scopus
  37. C. Caux, C. Massacrier, B. Vanbervliet et al., “Activation of human dendritic cells through CD40 cross-linking,” The Journal of Experimental Medicine, vol. 180, no. 4, pp. 1263–1272, 1994. View at Google Scholar · View at Scopus
  38. D. N. Hart and T. C. Prickett, “Intercellular adhesion molecule-2 (ICAM-2) expression on human dendritic cells,” Cellular Immunology, vol. 148, pp. 447–454, 1993. View at Google Scholar
  39. K. Inaba and R. M. Steinman, “Monoclonal antibodies to LFA-1 and to CD4 inhibit the mixed leukocyte reaction after the antigen-dependent clustering of dendritic cells and T lymphocytes,” The Journal of Experimental Medicine, vol. 165, no. 5, pp. 1403–1417, 1987. View at Google Scholar · View at Scopus
  40. T. C. R. Prickett, J. L. McKenzie, and D. N. J. Hart, “Adhesion molecules on human tonsil dendritic cells,” Transplantation, vol. 53, no. 2, pp. 483–490, 1992. View at Google Scholar · View at Scopus
  41. M. J. Bevan, “Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay,” The Journal of Experimental Medicine, vol. 143, pp. 1283–1288, 1976. View at Google Scholar
  42. M. J. Bevan, “Priming for a cytotoxic response to minor histocompatibility antigens: antigen specificity and failure to demonstrate a carrier effect,” Journal of Immunology, vol. 118, no. 4, pp. 1370–1374, 1977. View at Google Scholar · View at Scopus
  43. P. Brossart and M. J. Bevan, “Presentation of exogenous protein antigens on major histocompatability complex class I molecules by dendritic cells: pathway of presentation and regulation by cytokines,” Blood, vol. 90, no. 4, pp. 1594–1599, 1997. View at Google Scholar · View at Scopus
  44. C. Caux, C. Dezutter-Dambuyant, D. Schmit, and J. Banchereau, “GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells,” Nature, vol. 360, no. 6401, pp. 258–261, 1992. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. C. Caux, B. Vanbervliet, C. Massacrier et al., “CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNFα,” The Journal of Experimental Medicine, vol. 184, no. 2, pp. 695–706, 1996. View at Google Scholar · View at Scopus
  46. K. Inaba, M. Inaba, N. Romani et al., “Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor,” The Journal of Experimental Medicine, vol. 176, no. 6, pp. 1693–1702, 1992. View at Publisher · View at Google Scholar · View at Scopus
  47. J. H. Peters, H. Xu, J. Ruppert, D. Ostermeier, D. Friedrichs, and R. K. H. Gieseler, “Signals required for differentiating dendritic cells from human monocytes in vitro,” Advances in Experimental Medicine and Biology, vol. 329, pp. 275–280, 1993. View at Google Scholar
  48. N. Romani, S. Gruner, D. Brang et al., “Proliferating dendritic cell progenitors in human blood,” The Journal of Experimental Medicine, vol. 180, no. 1, pp. 83–93, 1994. View at Publisher · View at Google Scholar · View at Scopus
  49. F. Sallusto and A. Lanzavecchia, “Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α,” The Journal of Experimental Medicine, vol. 179, no. 4, pp. 1109–1118, 1994. View at Google Scholar · View at Scopus
  50. A. W. Lee, T. Truong, K. Bickham et al., “A clinical grade cocktail of cytokines and PGE2 results in uniform maturation of human monocyte-derived dendritic cells: implications for immunotherapy,” Vaccine, vol. 20, supplement 4, pp. A8–A22, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. J.-P. Carralot, B. Weide, O. Schoor et al., “Production and characterization of amplified tumor-derived cRNA libraries to be used as vaccines against metastatic melanomas,” Genetic Vaccines and Therapy, vol. 3, article 6, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. B. Scheel, R. Teufel, J. Probst et al., “Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA,” European Journal of Immunology, vol. 35, no. 5, pp. 1557–1566, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. B. Scheel, S. Aulwurm, J. Probst et al., “Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA,” European Journal of Immunology, vol. 36, no. 10, pp. 2807–2816, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. D. Boczkowski, S. K. Nair, D. Snyder, and E. Gilboa, “Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo,” The Journal of Experimental Medicine, vol. 184, no. 2, pp. 465–472, 1996. View at Google Scholar · View at Scopus
  55. C. Milazzo, V. L. Reichardt, M. R. Muller, F. Grunebach, and P. Brossart, “Induction of myeloma-specific cytotoxic T cells using dendritic cells transfected with tumor-derived RNA,” Blood, vol. 101, no. 3, pp. 977–982, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. A. Heiser, M. A. Maurice, D. R. Yancey, D. M. Coleman, P. Dahm, and J. Vieweg, “Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T-cell responses against antigens expressed by primary and metastatic tumors,” Cancer Research, vol. 61, no. 8, pp. 3388–3393, 2001. View at Google Scholar · View at Scopus
  57. F. Grunebach, K. Kayser, M. M. Weck, M. R. Muller, S. Appel, and P. Brossart, “Cotransfection of dendritic cells with RNA coding for HER-2/neu and 4-1BBL increases the induction of tumor antigen specific cytotoxic T lymphocytes,” Cancer Gene Therapy, vol. 12, no. 9, pp. 749–756, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. M. W. Onaitis, M. F. Kalady, S. Emani, Z. Abdel-Wahab, D. S. Tyler, and S. K. Pruitt, “CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy,” Surgery, vol. 134, no. 2, pp. 300–305, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. M. F. Kalady, M. W. Onaitis, S. Emani, Z. Abdel-Wahab, D. S. Tyler, and S. K. Pruitt, “Sequential delivery of maturation stimuli increases human dendritic cell IL-12 production and enhances tumor antigen-specific immunogenicity,” Journal of Surgical Research, vol. 116, no. 1, pp. 24–31, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. Z. Abdel-Wahab, R. Cisco, J. Dannull et al., “Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses,” Journal of Surgical Research, vol. 124, no. 2, pp. 264–273, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. M. F. Kalady, M. W. Onaitis, K. M. Padilla, S. Emani, D. S. Tyler, and S. K. Pruitt, “Enhanced dendritic cell antigen presentation in RNA-based immunotherapy,” Journal of Surgical Research, vol. 105, no. 1, pp. 17–24, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. T. Naka, M. Iwahashi, M. Nakamura et al., “Tumor vaccine therapy against recrudescent tumor using dendritic cells simultaneously transfected with tumor RNA and granulocyte macrophage colony-stimulating factor RNA,” Cancer Science, vol. 99, no. 2, pp. 407–413, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. S.-G. Kim, M.-Y. Park, C.-H. Kim et al., “Modification of CEA with both CRT and TAT PTD induces potent anti-tumor immune responses in RNA-pulsed DC vaccination,” Vaccine, vol. 26, no. 50, pp. 6433–6440, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. A. Heiser, D. Coleman, J. Dannull et al., “Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors,” Journal of Clinical Investigation, vol. 109, no. 3, pp. 409–417, 2002. View at Publisher · View at Google Scholar · View at Scopus
  65. M. A. Morse, S. K. Nair, D. Boczkowski et al., “The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer,” International Journal of Gastrointestinal Cancer, vol. 32, no. 1, pp. 1–6, 2002. View at Google Scholar · View at Scopus
  66. I. Bedrosian, R. Mick, S. Xu et al., “Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients,” Journal of Clinical Oncology, vol. 21, no. 20, pp. 3826–3835, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. L. Fong, D. Brockstedt, C. Benike, L. Wu, and E. G. Engleman, “Dendritic cells injected via different routes induce immunity in cancer patients,” Journal of Immunology, vol. 166, no. 6, pp. 4254–4259, 2001. View at Google Scholar · View at Scopus
  68. J. A. Kyte, L. Mu, S. Aamdal et al., “Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA,” Cancer Gene Therapy, vol. 13, no. 10, pp. 905–918, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. S. Dueland, L. J. Mu, G. Kvalheim et al., “Dendritic cells transfected with allo-tumor mRNA as cancer vaccine in treatment of hormone resistant prostate cancer patients,” Journal of Clinical Oncology, vol. 23, no. 16s, 2005, abstract no. 2541. View at Google Scholar
  70. I. J. M. de Vries, W. J. Lesterhuis, J. O. Barentsz et al., “Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy,” Nature Biotechnology, vol. 23, no. 11, pp. 1407–1413, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. A. Bonehill, A. M. T. Van Nuffel, J. Corthals et al., “Single-step antigen loading and activation of dendritic cells by mRNA electroporation for the purpose of therapeutic vaccination in melanoma patients,” Clinical Cancer Research, vol. 15, no. 10, pp. 3366–3375, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. Z. Su, J. Dannull, A. Heiser et al., “Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells,” Cancer Research, vol. 63, no. 9, pp. 2127–2133, 2003. View at Google Scholar · View at Scopus
  73. N. Rains, R. J. Cannan, W. Chen, and R. S. Stubbs, “Development of a dendritic cell (DC)-based vaccine for patients with advanced colorectal cancer,” Hepato-Gastroenterology, vol. 48, no. 38, pp. 347–351, 2001. View at Google Scholar · View at Scopus
  74. J. A. Wolff, R. W. Malone, P. Williams et al., “Direct gene transfer into mouse muscle in vivo,” Science, vol. 247, no. 4949, pp. 1465–1468, 1990. View at Google Scholar · View at Scopus
  75. P. Qiu, P. Ziegelhoffer, J. Sun, and N. S. Yang, “Gene gun delivery of mRNA in situ results in efficient transgene expression and genetic immunization,” Gene Therapy, vol. 3, no. 3, pp. 262–268, 1996. View at Google Scholar · View at Scopus
  76. R. W. Malone, P. L. Felgner, and I. M. Verma, “Cationic liposome-mediated RNA transfection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 16, pp. 6077–6081, 1989. View at Google Scholar · View at Scopus
  77. S. Espuelas, A. Roth, C. Thumann, B. Frisch, and F. Schuber, “Effect of synthetic lipopeptides formulated in liposomes on the maturation of human dendritic cells,” Molecular Immunology, vol. 42, no. 6, pp. 721–729, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. K. S. Korsholm, E. M. Agger, C. Foged et al., “The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes,” Immunology, vol. 121, no. 2, pp. 216–226, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. B. Scheell, S. Braedel, J. Probst et al., “Immunostimulating capacities of stabilized RNA molecules,” European Journal of Immunology, vol. 34, no. 2, pp. 537–547, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. J.-P. Carralot, J. Probst, I. Hoerr et al., “Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines,” Cellular and Molecular Life Sciences, vol. 61, no. 18, pp. 2418–2424, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. S. M. Schmidt, M. Haentschel, and M. R. Mueller, “Vaccinations with RNA coding for tumor associated antigens in advanced RCC patients—a phase I/II study,” Journal of Clinical Oncology, vol. 16, supplement, 2008, abstract no. 3017. View at Google Scholar
  82. B. Weide, C. Garbe, H.-G. Rammensee, and S. Pascolo, “Plasmid DNA- and messenger RNA-based anti-cancer vaccination,” Immunology Letters, vol. 115, no. 1, pp. 33–42, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  83. J. Dannull, Z. Su, D. Rizzieri et al., “Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells,” Journal of Clinical Investigation, vol. 115, no. 12, pp. 3623–3633, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  84. O. P. Kristiansen, Z. M. Larsen, and F. Pociot, “CTLA-4 in autoimmune diseases—a general susceptibility gene to autoimmunity?” Genes and Immunity, vol. 1, no. 3, pp. 170–184, 2000. View at Google Scholar · View at Scopus
  85. E. A. Tivol, F. Borriello, A. N. Schweitzer, W. P. Lynch, J. A. Bluestone, and A. H. Sharpe, “Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4,” Immunity, vol. 3, no. 5, pp. 541–547, 1995. View at Google Scholar · View at Scopus
  86. P. Waterhouse, J. M. Penninger, E. Timms et al., “Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4,” Science, vol. 270, no. 5238, pp. 985–988, 1995. View at Google Scholar · View at Scopus
  87. A. Ribas, L. H. Camacho, G. Lopez-Berestein et al., “Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206,” Journal of Clinical Oncology, vol. 23, no. 35, pp. 8968–8977, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  88. R. P. Sutmuller, L. M. van Duivenvoorde, E. van Elsas et al., “Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25+ regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses,” The Journal of Experimental Medicine, vol. 194, no. 6, pp. 823–832, 2001. View at Publisher · View at Google Scholar
  89. J. Vollmer, R. Weeratna, P. Payette et al., “Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities,” European Journal of Immunology, vol. 34, no. 1, pp. 251–262, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  90. J. Vollmer and A. M. Krieg, “Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists,” Advanced Drug Delivery Reviews, vol. 61, no. 3, pp. 195–204, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  91. B. G. Molenkamp, B. J. R. Sluijter, P. A. M. Van Leeuwen et al., “Local administration of PF-3512676 CpG-B instigates tumor-specific CD8+ T-cell reactivity in melanoma patients,” Clinical Cancer Research, vol. 14, no. 14, pp. 4532–4542, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. M. M. Hipp, N. Hilf, S. Walter et al., “Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses,” Blood, vol. 111, no. 12, pp. 5610–5620, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. S. K. Nair, M. Morse, D. Boczkowski et al., “Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells,” Annals of Surgery, vol. 235, no. 4, pp. 540–549, 2002. View at Publisher · View at Google Scholar · View at Scopus
  94. M. A. Morse, S. K. Nair, P. J. Mosca et al., “Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA,” Cancer Investigation, vol. 21, no. 3, pp. 341–349, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. D. A. Caruso, L. M. Orme, A. M. Neale et al., “Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer,” Neuro-Oncology, vol. 6, no. 3, pp. 236–246, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  96. D. A. Caruso, L. M. Orme, G. M. Amor et al., “Results of a phase I study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children with stage 4 neuroblastoma,” Cancer, vol. 103, no. 6, pp. 1280–1291, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  97. Z. Su, J. Dannull, B. K. Yang et al., “Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer,” Journal of Immunology, vol. 174, no. 6, pp. 3798–3807, 2005. View at Google Scholar · View at Scopus
  98. L. J. Mu, J. A. Kyte, G. Kvalheim et al., “Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients,” British Journal of Cancer, vol. 93, no. 7, pp. 749–756, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  99. B. Weide, S. Pascolo, B. Scheel et al., “Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients,” Journal of Immunotherapy, vol. 32, no. 5, pp. 498–507, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus