Abstract
Alphaviruses have several characteristics that make them attractive as gene therapy vectors such as transient and high-level expression of heterologous genes in a wide variety of host cells. The alphavirus vectors, Semliki Forest virus (SFV), Sindbis virus (SIN), and Venezuelan equine encephalitis virus (VEE), have been developed as gene expression vectors. Alphaviruses are positive-strand RNA viruses that can mediate efficient cytoplasmic gene expression in mammalian cells and trigger stress pathways in the cells they infect, culminating in the death of the host. The alphavirus RNA replication machinery has been engineered for high-level heterologous gene expression. Since an RNA virus vector cannot integrate into chromosomal DNA, concerns about cell transformation are reduced. Alphavirus vectors demonstrate promise for safe tumor-killing and tumor-specific immune responses. Recombinant alphavirus RNA replicons may facilitate gene therapy of cancer. This chapter covers the development and applications of alphavirus vectors for glioma immunotherapy.
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References
Agapov EV, Frolov I, Lindenbach BD et al (1998) Non-cytopathogenic Sindbis RNA vectors for heterologous gene expression. Proc Natl Acad Sci USA 95 : 12989–12994
Ahn HJ, Maruo S, Tomura M et al (1997) A mechanism underlying synergy between IL 12 and IFN-gamma-inducing factor in enhanced production of IFN-gamma. J Immunol 159 : 2125–2131
Ashley DM, Faiola B, Nair S et al (1997) Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors. J Exp Med 186 : 1177–1182
Barbulescu K, Becker C, Schlaak JF et al (1998) IL-12 and IL-18 differentially regulate the transcriptional activity of the human IFN-gamma promoter in primary CD4 + T lymphocytes. J Immunol 160 : 3642–3647
Berglund P, Sjoberg M, Garoff H et al (1993) Semliki Forest virus expression system : production of conditionally infectious recombinant particles. Biotechnology 11 : 916–920
Berglund P, Smerdou C, Fleeton MN et al (1998) Enhancing immune responses using suicidal DNA vaccines. Nat Biotechnol 16 : 562–565
Boczkowski D, Nair SK, Snyder D et al (1996) Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 184 : 465–472
Boorsma M, Nieba L, Koller D et al (2000) A temperature-regulated replicon-based DNA expression system. Nat Biotechnol 18 : 429–432
Celluzzi CM, Mayordomo JI, Storkus WJ et al (1996) Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity. J Exp Med 183 : 283–287
Check E (2002) Gene therapy : a tragic setback. Nature 420 : 116–118
Dubensky TW Jr, Driver DA, Polo JM et al (1996) Sindbis virus DNA-based expression vectors : utility for in vitro and in vivo gene transfer. J Virol 70 : 508–519
Ehrengruber MU, Renggli M, Raineteau O et al (2003) Semliki Forest virus A7 (74) transduces hippocampal neurons and glial cells in a temperature-dependent dual manner. J Neurovirol 9 : 16–28
Engelhardt JF, Yang Y, Stratford-Perricaudet LD et al (1993a) Direct gene transfer of human CFTR into human bronchial epithelia of xenografts with E1-deleted adenoviruses. Nat Genet 4 : 27–34
Engelhardt JF, Simon RH, Yang Y et al (1993b) Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates : biological efficacy study. Hum Gene Ther 4 : 759–769
Felgner PL, Ringold GM (1989) Cationic liposome-mediated transfection. Nature 337 : 387–388
Gardner JP, Frolov I, Perri S et al (2000) Infection of human dendritic cells by a sindbis virus replicon vector is determined by a single amino acid substitution in the E2 glycoprotein. J Virol 74 : 11849–11857
Graham A, Walker R, Baird P et al (2005) CNS gene therapy applications of the Semliki Forest Virus 1 vector are limited by neurotoxicity. Mol Ther 13 : 631–635
Hardy WR, Strauss JH (1989) Processing the nonstructural polyproteins of sindbis virus : nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans. J Virol 63 : 4653–4664
Helenius A, Morein B, Fries E et al (1978) Human (HLA-A and HLA-B) and murine (H-2K and H-2D) histocompatibility antigens are cell surface receptors for Semliki Forest virus. Proc Natl Acad Sci USA 75 : 3846–3850
Herweijer H, Latendresse JS, Williams P et al (1995) A plasmid-based self-amplifying Sindbis virus vector. Hum Gene Ther 6 : 1161–1167
Huang HV, Rice CM, Xiong C et al (1989) RNA viruses as gene expression vectors. Virus Genes 3 : 85–91
Kobayashi M, Fitz L, Ryan M et al (1989) Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 170 : 827–845
Kohno K, Kataoka J, Ohtsuki T et al (1997) IFN--inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J Immunol 158 : 1541–1550
Kohno A, Emi N, Kasai M et al (1998) Semliki Forest virus-based DNA expression vector : transient protein production followed by cell death. Gene Ther 5 : 415–418
Kohyama M, Saijyo K, Hayasida M et al (1998) Direct activation of human CD8 + cytotoxic T lymphocytes by interleukin-18. Jpn J Cancer Res 89 : 1041–1046
Leitner WW, Ying H, Driver DA et al (2000) Enhancement of tumor-specific immune response with plasmid DNA replicon vectors. Cancer Res 60 : 51–55
Leitner WW, Hwang LN, deVeer MJ et al (2003) Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways. Nat Med 9 : 33–39
Levis R, Huang H, Schlesinger S (1987) Engineered defective interfering RNAs of Sindbis virus express bacterial chloramphenicol acetyltransferase in avian cells. Proc Natl Acad Sci USA 84 : 4811–4815
Levis R, Schlesinger S, Huang HV (1990) Promoter for Sindbis virus RNA-dependent subgenomic RNA transcription. J Virol 64 : 1726–1733
Lewis J, Wesselingh SL, Griffin DE et al (1996) Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence. J Virol 70 : 1828–1835
Liljestrom P, Garoff H (1991) A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology 9 : 1356–1361
London SD, Schmaljohn AL, Dalrymple JM et al (1992) Infectious enveloped RNA virus antigenic chimeras. Proc Natl Acad Sci USA 89 : 207–211
Lundstrom K (2003) Latest development of viral vectors for gene therapy. Trends Biotechnol 21 : 117–122
Lundstrom K, Abenavoli A, Malgaroli A et al (2003) Novel Semliki Forest virus vectors with reduced cytotoxicity and temperature sensitivity for long-term enhancement of transgene expression. Mol Ther 7 : 202–209
Manetti R, Parronchi P, Giudizi MG et al (1993) Natural killer cell stimulatory factor (interleukin 12 (IL-12)) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med 177 : 1199–1204
Mayordomo JI, Zorina T, Storkus WJ et al (1995) Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat Med 1 : 1297–1302
Mulligan RC (1993) The basic science of gene therapy. Science 260 : 926–932
Ni B, Lin Z, Zhou L et al (2004) Induction of P815 tumor immunity by DNA-based recombinant Semliki Forest virus or replicon DNA expressing the P1A gene. Cancer Detect Prev 28 : 418–425
Ohno K, Sawai K, Iijima Y et al (1997) Cell specific targeting of Sindbis virus vectors displaying IgG binding domains of protein A. Nat Biotechnol 15 : 763–767
Okamura H, Tsutusui H, Komatsu T et al (1995) Cloning of a new cytokine that induces IFN- production by T cells. Nature 378 : 88–91
Piper RC, Slot JW, Li G, et al (1994) Recombinant Sindbis virus as an expression system for cell biology. Methods Cell Biol 43 : 55–78
Polo JM, Belli BA, Driver DA et al (1999) Stable alphavirus packaging cell lines for Sindbis virus- and Semliki Forest virus-derived vectors. Proc Natl Acad Sci USA 96 : 4598–4603
Porgador A, Gilboa E (1995) Bone marrow-generated dendritic cells pulsed with a class I restricted peptide are potent inducers of cytotoxic T lymphocytes. J Exp Med 182 : 255–260
Rabinowitz JE, Samulski J (1998) Adeno-associated virus expression systems for gene transfer. Curr Opin Biotechnol 9 : 470–475
Ren H, Boulikas T, Lundstrom K et al (2003) Immunogene therapy of recurrent glioblastoma multiforme with a liposomally encapsulated replication-incompetent Semliki forest virus vector carrying the human interleukin-12 gene-a phase I/II clinical protocol. J Neurooncol 64 : 147–154
Rosenfeld MA, Siegfried W, Yoshimura K et al (1991) Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science 252 : 431–434
Sammin DJ, Butler D, Atkins GJ et al (1999) Cell death mechanisms in the olfactory bulb of rats infected intranasally with Semliki forest virus. Neuropathol Appl Neurobiol 25 : 236–243
Sawai K, Meruelo D (1998) Cell-specific transfection of choriocarcinoma cells by using Sindbis virus hCG expressing chimeric vector. Biochem Biophys Res Commun 248 : 315–323
Sawai K, Ohno K, Iijima Y et al (1998) A novel method of cell-specific mRNA transfection. Mol Genet Metab 64 : 44–51
Schlesinger S, Schlesinger MJ (1996) Togaviridae : the viruses and their replication. In : Fields BN, Knipe PM (eds) Fields virology, 3rd edn. Lippincott-Raven, New York
Steinman RM, Pack M, Inaba K (1997) Dendritic cells in the T-cell areas of lymphoid organs. Immunol Rev 156 : 25–37
Smerdou C, Liljestrom P (1999) Two-helper RNA system for production of recombinant Semliki forest virus particles. J Virol 73 : 1092–1098
Strauss EG, Strauss JH (1986) Structure and Replication of the Alphavirus Genome. In : Schlesinger S, Schlesinger MJ (eds) The Togaviridae and Flaviviridae, 3rd edn. Plenum, New York
Strauss JH, Strauss EG (1994) The alphaviruses : gene expression, replication, and evolution. Microbiol Rev 58 : 491–562
Unno Y, Shino Y, Kondo F et al (2005) Oncolytic viral therapy for cervical and ovarian cancer cells by Sindbis virus AR339 strain. Clin Cancer Res 11 : 4553–4560
Vaha-Koskela MJ, Tuittila MT, Nygardas PT et al (2003) A novel neurotropic expression vector based on the avirulent A7 (74) strain of Semliki Forest virus. J Neurovirol 9 : 1–15
Wahlfors JJ, Morgan RA (1999) Production of minigene-containing retroviral vectors using an alphavirus/retrovirus hybrid vector system. Hum Gene Ther 10 : 1197–1206
Wahlfors JJ, Xanthopoulos KG, Morgan RA (1997) Semliki Forest virus-mediated production of retroviral vector RNA in retroviral packaging cells. Hum Gene Ther 8 : 2031–2041
Wang KS, Kuhn RJ, Strauss EG et al (1992) High-affinity laminin receptor is a receptor for Sindbis virus in mammalian cells. J Virol 66 : 4992–5001
Willems WR, Kaluza G, Boschek CB et al (1979) Semliki forest virus : cause of a fatal case of human encephalitis. Science 203 : 1127–1129
Xiong C, Levis R, Shen P et al (1989) Sindbis virus : an efficient, broad host range vector for gene expression in animal cells. Science 243 : 1188–1191
Yamanaka R, Xanthopoulos KG (2004) Development of improved Sindbis virus-based DNA expression vector. DNA Cell Biol 23 : 75–80
Yamanaka R, Xanthopoulos KG (2005) Induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis DNA encoding gp100 and IL-18. DNA Cell Biol 24 : 317–324
Yamanaka R, Zullo SA, Tanaka R et al (2001) Enhancement of antitumor immune response in glioma models in mice by genetically modified dendritic cells pulsed with Semliki forest virus-mediated complementary DNA. J Neurosurg 94 : 474–481
Yamanaka R, Yajima N, Tsuchiya N et al (2002) Administration of interleukin-12 and -18 enhancing the antitumor immunity of genetically modified dendritic alls that had been pulsed with Senlik; forest virus-mediated tumor complementary RNA. J Neurosurg 97:1184–1190
Yamanaka R (2008) Alpha viruses. In: Harrington KJ, Vile RG, Pandha HS (eds) Viral therapy of cancer. Wiley, Chichester
Ying H, Zaks TZ, Wang RF et al (1999) Cancer therapy using a self-replicating RNA vaccine. Nat Med 5 : 823–827
Zhang J, Asselin-Paturel C, Bex F et al (1997a) Cloning of human IL-12 p40 and p35 DNA into the Semliki Forest virus vector : expression of IL-12 in human tumor cells. Gene Ther 4 : 367–374
Zitvogel L, Mayordomo JI, Tjandrawan T et al (1996) Therapy of murine tumors with tumor peptide-pulsed dendritic cells : dependence on T cells, B7 costimulation, and T helper cell 1- associated cytokines. J Exp Med 183 : 87–97
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Yamanaka, R. (2009). Immunotherapeutic Approach for Glioma by Alphaviruses as Positive Strand RNA Viruses. In: Erdmann, V., Reifenberger, G., Barciszewski, J. (eds) Therapeutic Ribonucleic Acids in Brain Tumors. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00475-9_6
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DOI: https://doi.org/10.1007/978-3-642-00475-9_6
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