Thérapie génique du cancer du foie : le point

  • G. Gonzalez-Aseguinolaza
  • J. Prieto
  • R. Hernandez-Alcoceba
Review Article / Article de Synthèse
  • 109 Downloads

Résumé

Le cancer du foie est l’une des maladies les plus importantes au monde, en raison de sa haute incidence et de sa résistance notable aux traitements classiques. Le carcinome hépatocellulaire (CHC) représente plus de 80 % des cancers primitifs du foie. Le poids du CHC en Afrique est remarquable, car certains des facteurs étiologiques majeurs, tels que l’hépatite B chronique et l’exposition aux mycotoxines, sont particulièrement fréquents dans ce continent. Outre le besoin urgent de campagnes de prévention, il faut de nouvelles armes thérapeutiques pour améliorer la prise en charge des patients atteints de CHC. La thérapie génique (TG) est une discipline expérimentale en évolution rapide, qui vise à surmonter les obstacles importants identifiés dans les premiers essais cliniques. Malgré les difficultés particulières inhérentes au transfert de gènes dans des tumeurs, le cancer reste l’un des principaux domaines d’application de la TG. Les récents progrès scientifiques et techniques en TG et en thérapie mixte généticocellulaire, associés aux nouvelles techniques de radiothérapie et d’immunothérapie chez les patients atteints de CHC, ouvrent de nouvelles perspectives dans ce domaine. Nous résumons ici les tendances actuelles de la TG pour le traitement du CHC.

Mots clés

Foie Cancer Carcinome hépatocellulaire Thérapie génique 

Gene therapy of liver cancer: an update

Abstract

Liver cancer is one of the most important health problems worldwide, due to its high incidence and remarkable resistance to conventional treatments. Hepatocellular carcinoma (HCC) accounts for more than 80% of the primary liver cancers. The burden of HCC in Africa is remarkable because some of the major etiologic factors, such as chronic hepatitis B infection and exposure to mycotoxins are particularly frequent in this continent. Besides the urgent need for prevention campaigns, new therapeutic options are needed to improve the management of HCC patients. Gene therapy (GT) is an experimental discipline that is rapidly evolving to solve the important obstacles identified in early clinical trials. Despite the particular difficulties inherent in the transfer of genes into tumors, cancer is still one of the most frequent applications of GT. Recent technical and scientific advances in gene therapy and combined cell and gene therapy, together with new radiotherapy techniques and immunotherapy in patients with HCC have opened new possibilities in this field. Here we summarize the actual trends in GT approaches for the treatment of HCC.

Keywords

Liver Cancer Hepatocelullar carcinoma Gene therapy 

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References

  1. 1.
    El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576PubMedGoogle Scholar
  2. 2.
    Yuen MF, Hou JL, Chutaputti A (2009) Hepatocellular carcinoma in the Asia pacific region. J Gastroenterol Hepatol 24:346–353PubMedGoogle Scholar
  3. 3.
    Parkin DM, Sitas F, Chirenje M, et al (2008) Part I: cancer in Indigenous Africans: burden, distribution, and trends. Lancet Oncol 9:683–692PubMedGoogle Scholar
  4. 4.
    Parkin DM (2006) The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118:3030–3044PubMedGoogle Scholar
  5. 5.
    Mendy M, Walton R (2009) Molecular pathogenesis and early detection of hepatocellular carcinoma: perspectives from West Africa. Cancer Lett 286:44–51PubMedGoogle Scholar
  6. 6.
    El-Serag HB, Marrero JA, Rudolph L, et al (2008) Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology 134:1752–1763PubMedGoogle Scholar
  7. 7.
    Mintzer MA, Simanek EE (2009) Nonviral vectors for gene delivery. Chem Rev 109:259–302PubMedGoogle Scholar
  8. 8.
    Bouard D, Alazard-Dany D, Cosset FL (2009) Viral vectors: from virology to transgene expression. Br J Pharmacol 157:153–165PubMedGoogle Scholar
  9. 9.
    Dean NM, Bennett CF (2003) Antisense oligonucleotide-based therapeutics for cancer. Oncogene 22:9087–9096PubMedGoogle Scholar
  10. 10.
    Li QX, Tan P, Ke N, et al (2007) Ribozyme technology for cancer gene target identification and validation. Adv Cancer Res 96:103–143PubMedGoogle Scholar
  11. 11.
    Song MS, Lee SW (2006) Cancer-selective induction of cytotoxicity by tissue-specific expression of targeted trans-splicing ribozyme. FEBS Lett 580:5033–5043PubMedGoogle Scholar
  12. 12.
    Pai SI, Lin YY, Macaes B, et al (2006) Prospects of RNA interference therapy for cancer. Gene Ther 13:464–477PubMedGoogle Scholar
  13. 13.
    Arbuthnot P, Thompson LJ (2008) Harnessing the RNA interference pathway to advance treatment and prevention of hepatocellular carcinoma. World J Gastroenterol 14:1670–1681PubMedGoogle Scholar
  14. 14.
    Hannon GJ, Rossi JJ (2004) Unlocking the potential of the human genome with RNA interference. Nature 431:371–378PubMedGoogle Scholar
  15. 15.
    Weinberg MS, Ely A, Barichievy S, et al (2007) Specific inhibition of HBV replication in vitro and in vivo with expressed long hairpin RNA. Mol Ther 15:534–541PubMedGoogle Scholar
  16. 16.
    Morrissey DV, Lockridge JA, Shaw L, et al (2005) Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23:1002–1007PubMedGoogle Scholar
  17. 17.
    Liu SX, Sun WS, Cao YL, et al (2004) Antisense oligonucleotide targeting at the initiator of hTERT arrests growth of hepatoma cells. World J Gastroenterol 10:366–370PubMedGoogle Scholar
  18. 18.
    Guo X, Wang W, Zhou F, et al (2008) siRNA-mediated inhibition of hTERT enhances chemosensitivity of hepatocellular carcinoma. Cancer Biol Ther 7:1555–1560PubMedGoogle Scholar
  19. 19.
    Jiang Y, Zhou XD, Liu YK, et al (2004) Antisense Tcf inhibits the neoplastic growth of liver cancer cells. J Cancer Res Clin Oncol 130:671–678PubMedGoogle Scholar
  20. 20.
    Sangkhathat S, Kusafuka T, Miao J, et al (2006) In vitro RNA interference against beta-catenin inhibits the proliferation of pediatric hepatic tumors. Int J Oncol 28:715–722PubMedGoogle Scholar
  21. 21.
    Hu J, Dong A, Fernandez-Ruiz V, et al (2009) Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res 69:6951–6959PubMedGoogle Scholar
  22. 22.
    Cho-Rok J, Yoo J, Jang YJ, et al (2006) Adenovirus-mediated transfer of siRNA against PTTG1 inhibits liver cancer cell growth in vitro and in vivo. Hepatology 43:1042–1052PubMedGoogle Scholar
  23. 23.
    Li H, Fu X, Chen Y, et al (2005) Use of adenovirus-delivered siRNA to target oncoprotein p28GANK in hepatocellular carcinoma. Gastroenterology 128:2029–2041PubMedGoogle Scholar
  24. 24.
    Li WC, Ye SL, Sun RX, et al (2006) Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res 12:7140–7148PubMedGoogle Scholar
  25. 25.
    Zhang R, Ma L, Zheng M, et al (2009) Survivin knockdown by short hairpin RNA abrogates the growth of human hepatocellular carcinoma xenografts in nude mice. Cancer Gene Ther 17(4):275–278PubMedGoogle Scholar
  26. 26.
    Zhu DE, Hoti N, Song Z, et al (2006) Suppression of tumor growth using a recombinant adenoviral vector carrying the dominant-negative mutant gene Survivin-D53A in a nude mice model. Cancer Gene Ther 13:762–770PubMedGoogle Scholar
  27. 27.
    Sun X, Jiang H, Jiang X, et al (2009) Antisense hypoxiainducible factor-1alpha augments transcatheter arterial embolization in the treatment of hepatocellular carcinomas in rats. Hum Gene Ther 20:314–324PubMedGoogle Scholar
  28. 28.
    Giovannini C, Gramantieri L, Chieco P, et al (2009) Selective ablation of Notch3 in HCC enhances doxorubicin’s death promoting effect by a p53 dependent mechanism. J Hepatol 50:969–979PubMedGoogle Scholar
  29. 29.
    Mucha SR, Rizzani A, Gerbes AL, et al (2009) JNK inhibition sensitises hepatocellular carcinoma cells but not normal hepatocytes to the TNF-related apoptosis-inducing ligand. Gut 58:688–698PubMedGoogle Scholar
  30. 30.
    He SQ, Rehman H, Gong MG, et al (2007) Inhibiting survivin expression enhances TRAIL-induced tumoricidal activity in human hepatocellular carcinoma via cell cycle arrest. Cancer Biol Ther 6:1247–1257PubMedGoogle Scholar
  31. 31.
    Graff JR, Konicek BW, Vincent TM, et al (2007) Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity. J Clin Invest 117:2638–2648PubMedGoogle Scholar
  32. 32.
    Guan YS, La Z, Yang L, et al (2007) p53 gene in treatment of hepatic carcinoma: status quo. World J Gastroenterol 13:985–992PubMedGoogle Scholar
  33. 33.
    Zender L, Kock R, Eckhard M, et al (2002) Gene therapy by intrahepatic and intratumoral trafficking of p53-VP22 induces regression of liver tumors. Gastroenterology 123:608–618PubMedGoogle Scholar
  34. 34.
    Miettinen S, Ylikomi T (2009) Concomitant exposure of ovarian cancer cells to docetaxel, CPT-11 or SN-38 and adenovirus-mediated p53 gene therapy. Anticancer Drugs 20:589–600PubMedGoogle Scholar
  35. 35.
    Idogawa M, Sasaki Y, Suzuki H, et al (2009) A single recombinant adenovirus expressing p53 and p21-targeting artificial microRNAs efficiently induces apoptosis in human cancer cells. Clin Cancer Res 15:3725–3732PubMedGoogle Scholar
  36. 36.
    Peng Z (2005) Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. Hum Gene Ther 16:1016–1027PubMedGoogle Scholar
  37. 37.
    Yang ZX, Wang D, Wang G, et al (2009) Clinical study of recombinant adenovirus-p53 combined with fractionated stereotactic radiotherapy for hepatocellular carcinoma. J Cancer Res Clin OncolGoogle Scholar
  38. 38.
    Yin C, Lin Y, Zhang X, et al (2008) Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4alpha gene. Hepatology 48:1528–1539PubMedGoogle Scholar
  39. 39.
    Fong S, Itahana Y, Sumida T, et al (2003) Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis. Proc Natl Acad Sci U S A 100:13543–13548PubMedGoogle Scholar
  40. 40.
    Gho JW, Ip WK, Chan KY, et al (2008) Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest. Cancer Res 68:6743–6751PubMedGoogle Scholar
  41. 41.
    Ji J, Shi J, Budhu A, et al (2009) MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 361:1437–1447PubMedGoogle Scholar
  42. 42.
    Kota J, Chivukula RR, O’Donnell KA, et al (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137:1005–1017PubMedGoogle Scholar
  43. 43.
    Fornari F, Gramantieri L, Giovannini C, et al (2009) MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 69:5761–5767PubMedGoogle Scholar
  44. 44.
    Xu T, Zhu Y, Xiong Y, et al (2009) MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology 50:113–121PubMedGoogle Scholar
  45. 45.
    Su H, Yang JR, Xu T, et al (2009) MicroRNA-101, downregulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res 69:1135–1142PubMedGoogle Scholar
  46. 46.
    Abdul-Ghani R, Ohana P, Matouk I, et al (2000) Use of transcriptional regulatory sequences of telomerase (hTER and hTERT) for selective killing of cancer cells. Mol Ther 2:539–544PubMedGoogle Scholar
  47. 47.
    Kunitomi M, Takayama E, Suzuki S, et al (2000) Selective inhibition of hepatoma cells using diphtheria toxin A under the control of the promoter/enhancer region of the human alphafetoprotein gene. Jpn J Cancer Res 91:343–350PubMedGoogle Scholar
  48. 48.
    Koshikawa N, Takenaga K (2005) Hypoxia-regulated expression of attenuated diphtheria toxin A fused with hypoxia-inducible factor-1alpha oxygen-dependent degradation domain preferentially induces apoptosis of hypoxic cells in solid tumor. Cancer Res 65:11622–11630PubMedGoogle Scholar
  49. 49.
    de Vries EG, Gietema JA, de Jong S (2006) Tumor necrosis factor-related apoptosis-inducing ligand pathway and its therapeutic implications. Clin Cancer Res 12:2390–2393PubMedGoogle Scholar
  50. 50.
    Zhang Y, Ma H, Zhang J, et al (2008) AAV-mediated TRAIL gene expression driven by hTERT promoter suppressed human hepatocellular carcinoma growth in mice. Life Sci 82:1154–1161PubMedGoogle Scholar
  51. 51.
    Wang Y, Huang F, Cai H, et al (2008) Potent antitumor effect of TRAIL mediated by a novel adeno-associated viral vector targeting to telomerase activity for human hepatocellular carcinoma. J Gene Med 10:518–526PubMedGoogle Scholar
  52. 52.
    Shi J, Liu Y, Zheng Y, et al (2006) Therapeutic expression of an anti-death receptor 5 single-chain fixed-variable region prevents tumor growth in mice. Cancer Res 66:11946–11953PubMedGoogle Scholar
  53. 53.
    Vassaux G, Martin-Duque P (2004) Use of suicide genes for cancer gene therapy: study of the different approaches. Expert Opin Biol Ther 4:519–530PubMedGoogle Scholar
  54. 54.
    Suzuki T, Sakurai F, Nakamura S, et al (2008) miR-122a-regulated expression of a suicide gene prevents hepatotoxicity without altering antitumor effects in suicide gene therapy. Mol Ther 16:1719–1726PubMedGoogle Scholar
  55. 55.
    Fillat C, Carrio M, Cascante A, et al (2003) Suicide gene therapy mediated by the Herpes Simplex virus thymidine kinase gene/Ganciclovir system: fifteen years of application. Curr Gene Ther 3:13–26PubMedGoogle Scholar
  56. 56.
    Penuelas I, Mazzolini G, Boan JF, et al (2005) Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology 128:1787–1795PubMedGoogle Scholar
  57. 57.
    Li N, Zhou J, Weng D, et al (2007) Adjuvant adenovirusmediated delivery of herpes simplex virus thymidine kinase administration improves outcome of liver transplantation in patients with advanced hepatocellular carcinoma. Clin Cancer Res 13:5847–5854PubMedGoogle Scholar
  58. 58.
    Kan O, Kingsman S, Naylor S (2002) Cytochrome P450-based cancer gene therapy: current status. Expert Opin Biol Ther 2:857–868PubMedGoogle Scholar
  59. 59.
    Palmer DH, Mautner V, Mirza D, et al (2004) Virus-directed enzyme prodrug therapy: intratumoral administration of a replication-deficient adenovirus encoding nitroreductase to patients with resectable liver cancer. J Clin Oncol 22:1546–1552PubMedGoogle Scholar
  60. 60.
    Li J, Li H, Zhu L, et al (2010) The adenovirus-mediated linamarase/linamarin suicide system: a potential strategy for the treatment of hepatocellular carcinoma. Cancer Lett 289:217–227PubMedGoogle Scholar
  61. 61.
    Kievit E, Bershad E, Ng E, et al (1999) Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts. Cancer Res 59:1417–1421PubMedGoogle Scholar
  62. 62.
    Graepler F, Lemken ML, Wybranietz WA, et al (2005) Bifunctional chimeric SuperCD suicide gene -YCD: YUPRT fusion is highly effective in a rat hepatoma model. World J Gastroenterol 11:6910–6919PubMedGoogle Scholar
  63. 63.
    Lemken ML, Graepler F, Wolf C, et al (2007) Fusion of HSV-1 VP22 to a bifunctional chimeric SuperCD suicide gene compensates for low suicide gene transduction efficiencies. Int J Oncol 30:1153–1161PubMedGoogle Scholar
  64. 64.
    Kang JH, Chung JK, Lee YJ, et al (2004) Establishment of a human hepatocellular carcinoma cell line highly expressing sodium iodide symporter for radionuclide gene therapy. J Nucl Med 45:1571–1576PubMedGoogle Scholar
  65. 65.
    Faivre J, Clerc J, Gerolami R, et al (2004) Long-term radioiodine retention and regression of liver cancer after sodium iodide symporter gene transfer in wistar rats. Cancer Res 64:8045–8051PubMedGoogle Scholar
  66. 66.
    Herve J, Cunha AS, Liu B, et al (2008) Internal radiotherapy of liver cancer with rat hepatocarcinoma-intestine-pancreas gene as a liver tumor-specific promoter. Hum Gene Ther 19:915–926PubMedGoogle Scholar
  67. 67.
    Ivy SP, Wick JY, Kaufman BM (2009) An overview of smallmolecule inhibitors of VEGFR signaling. Nat Rev Clin Oncol 6:569–579PubMedGoogle Scholar
  68. 68.
    Cao Y, Ji RW, Davidson D, et al (1996) Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells. J Biol Chem 271:29461–22467Google Scholar
  69. 69.
    Torimura T, Ueno T, Kin M, et al (2006) Gene transfer of kringle 1-5 suppresses tumor development and improves prognosis of mice with hepatocellular carcinoma. Gastroenterology 130:1301–1310PubMedGoogle Scholar
  70. 70.
    Lee K, Yun ST, Kim YG, et al (2006) Adeno-associated virusmediated expression of apolipoprotein (a) kringles suppresses hepatocellular carcinoma growth in mice. Hepatology 43:1063–1073PubMedGoogle Scholar
  71. 71.
    Shen Z, Yang ZF, Gao Y, et al (2008) The kringle 1 domain of hepatocyte growth factor has antiangiogenic and antitumor cell effects on hepatocellular carcinoma. Cancer Res 68:404–414PubMedGoogle Scholar
  72. 72.
    Tse LY, Sun X, Jiang H, et al (2008) Adeno-associated virusmediated expression of kallistatin suppresses local and remote hepatocellular carcinomas. J Gene Med 10:508–517PubMedGoogle Scholar
  73. 73.
    Dawson DW, Volpert OV, Gillis P, et al (1999) Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285:245–248PubMedGoogle Scholar
  74. 74.
    Matsumoto K, Ishikawa H, Nishimura D, et al (2004) Antiangiogenic property of pigment epithelium-derived factor in hepatocellular carcinoma. Hepatology 40:252–259PubMedGoogle Scholar
  75. 75.
    Jiang H, Meng Q, Tan H, et al (2007) Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas. Int J Cancer 121:416–424PubMedGoogle Scholar
  76. 76.
    Andrews KJ, Ribas A, Butterfield LH, et al (2000) Adenovirusinterleukin-12-mediated tumor regression in a murine hepatocellular carcinoma model is not dependent on CD1-restricted natural killer T cells. Cancer Res 60:6457–664PubMedGoogle Scholar
  77. 77.
    Barajas M, Mazzolini G, Genove G, et al (2001) Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12. Hepatology 33:52–61PubMedGoogle Scholar
  78. 78.
    Waehler R, Ittrich H, Mueller L, et al (2005) Low-dose adenoviral immunotherapy of rat hepatocellular carcinoma using singlechain interleukin-12. Hum Gene Ther 16:307–317PubMedGoogle Scholar
  79. 79.
    Huang KW, Huang YC, Tai KF, et al (2008) Dual therapeutic effects of interferon-alpha gene therapy in a rat hepatocellular carcinoma model with liver cirrhosis. Mol Ther 16:1681–1687PubMedGoogle Scholar
  80. 80.
    Baratin M, Ziol M, Romieu R, et al (2001) Regression of primary hepatocarcinoma in cancer-prone transgenic mice by local interferon-gamma delivery is associated with macrophages recruitment and nitric oxide production. Cancer Gene Ther 8:193–202PubMedGoogle Scholar
  81. 81.
    Cao G, Kuriyama S, Du P, et al (1997) Complete regression of established murine hepatocellular carcinoma by in vivo tumor necrosis factor alpha gene transfer. Gastroenterology 112:501–510PubMedGoogle Scholar
  82. 82.
    Tai KF, Chen PJ, Chen DS, et al (2003) Concurrent delivery of GM-CSF and endostatin genes by a single adenoviral vector provides a synergistic effect on the treatment of orthotopic liver tumors. J Gene Med 5:386–398PubMedGoogle Scholar
  83. 83.
    Liang CM, Zhong CP, Sun RX, et al (2007) Local expression of secondary lymphoid tissue chemokine delivered by adeno-associated virus within the tumor bed stimulates strong anti-liver tumor immunity. J Virol 81:9502–911PubMedGoogle Scholar
  84. 84.
    Sangro B, Mazzolini G, Ruiz J, et al (2004) Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors. J Clin Oncol 22:1389–1397PubMedGoogle Scholar
  85. 85.
    Guan M, Rodriguez-Madoz JR, Alzuguren P, et al (2006) Increased efficacy and safety in the treatment of experimental liver cancer with a novel adenovirus-alphavirus hybrid vector. Cancer Res 66:1620–1629PubMedGoogle Scholar
  86. 86.
    Wang L, Hernandez-Alcoceba R, Shankar V, et al (2004) Prolonged and inducible transgene expression in the liver using gutless adenovirus: a potential therapy for liver cancer. Gastroenterology 126:278–289PubMedGoogle Scholar
  87. 87.
    Crettaz J, Otano I, Ochoa L, et al (2009) Treatment of chronic viral hepatitis in woodchucks by prolonged intrahepatic expression of interleukin-12. J Virol 83:2663–2674PubMedGoogle Scholar
  88. 88.
    Zabala M, Alzuguren P, Benavides C, et al (2009) Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy. Mol Cancer 8:2PubMedGoogle Scholar
  89. 89.
    Chen X, Lin X, Zhao J, et al (2008) A tumor-selective biotherapy with prolonged impact on established metastases based on cytokine gene-engineered MSCs. Mol Ther 16:749–756PubMedGoogle Scholar
  90. 90.
    Rodriguez-Madoz JR, Liu KH, Quetglas JI, et al (2009) Semliki forest virus expressing interleukin-12 induces antiviral and antitumoral responses in woodchucks with chronic viral hepatitis and hepatocellular carcinoma. J Virol 83:12266–12278PubMedGoogle Scholar
  91. 91.
    Xiao H, Huang B, Yuan Y, et al (2007) Soluble PD-1 facilitates 4-1BBL-triggered antitumor immunity against murine H22 hepatocarcinoma in vivo. Clin Cancer Res 13:1823–1830PubMedGoogle Scholar
  92. 92.
    Chang CJ, Chen YH, Huang KW, et al (2007) Combined GMCSF and IL-12 gene therapy synergistically suppresses the growth of orthotopic liver tumors. Hepatology 45:746–754PubMedGoogle Scholar
  93. 93.
    Comes A, Di Carlo E, Musiani P, et al (2002) IFN-gamma-independent synergistic effects of IL-12 and IL-15 induce anti-tumor immune responses in syngeneic mice. Eur J Immunol 32:1914–1923PubMedGoogle Scholar
  94. 94.
    Martinet O, Ermekova V, Qiao JQ, et al (2000) Immunomodulatory gene therapy with interleukin 12 and 4-1BB ligand: longterm remission of liver metastases in a mouse model. J Natl Cancer Inst 92:931–936PubMedGoogle Scholar
  95. 95.
    Putzer BM, Stiewe T, Rodicker F, et al (2001) Large nontransplanted hepatocellular carcinoma in woodchucks: treatment with adenovirus-mediated delivery of interleukin 12/B7.1 genes. J Natl Cancer Inst 93:472–479PubMedGoogle Scholar
  96. 96.
    Iida T, Shiba H, Misawa T, et al (2008) Adenovirus-mediated CD40L gene therapy induced both humoral and cellular immunity against rat model of hepatocellular carcinoma. Cancer Sci 99:2097–2103PubMedGoogle Scholar
  97. 97.
    Narvaiza I, Mazzolini G, Barajas M, et al (2000) Intratumoral coinjection of two adenoviruses, one encoding the chemokine IFN-gamma-inducible protein-10 and another encoding IL-12, results in marked antitumoral synergy. J Immunol 164:3112–3122PubMedGoogle Scholar
  98. 98.
    Chen WY, Cheng YT, Lei HY, et al (2005) IL-24 inhibits the growth of hepatoma cells in vivo. Genes Immun 6:493–499PubMedGoogle Scholar
  99. 99.
    Yang YJ, Chen DZ, Li LX, et al (2009) Targeted IL-24 gene therapy inhibits cancer recurrence after liver tumor resection by inducing tumor cell apoptosis in nude mice. Hepatobiliary Pancreat Dis Int 8:174–178PubMedGoogle Scholar
  100. 100.
    Hu P, Hu HD, Chen M, et al (2009) Expression of interleukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma. Mol Immunol 46:1654–1662PubMedGoogle Scholar
  101. 101.
    Grimm CF, Ortmann D, Mohr L, et al (2000) Mouse alphafetoprotein-specific DNA-based immunotherapy of hepatocellular carcinoma leads to tumor regression in mice. Gastroenterology 119:1104–1112PubMedGoogle Scholar
  102. 102.
    Saeki A, Nakao K, Nagayama Y, et al (2004) Diverse efficacy of vaccination therapy using the alpha-fetoprotein gene against mouse hepatocellular carcinoma. Int J Mol Med 13:111–116PubMedGoogle Scholar
  103. 103.
    Rodriguez MM, Ryu SM, Qian C, et al (2008) Immunotherapy of murine hepatocellular carcinoma by alpha-fetoprotein DNA vaccination combined with adenovirus-mediated chemokine and cytokine expression. Hum Gene Ther 19:753–759PubMedGoogle Scholar
  104. 104.
    Peron JM, Couderc B, Rochaix P, et al (2004) Treatment of murine hepatocellular carcinoma using genetically modified cells to express interleukin-12. J Gastroenterol Hepatol 19:388–396PubMedGoogle Scholar
  105. 105.
    Vollmer CM Jr, Eilber FC, Butterfield LH, et al (1999) Alphafetoprotein-specific genetic immunotherapy for hepatocellular carcinoma. Cancer Res 59:3064–3067PubMedGoogle Scholar
  106. 106.
    Yang JY, Cao DY, Xue Y, et al (2010) Improvement of dendritic-based vaccine efficacy against hepatitis B virusrelated hepatocellular carcinoma by two tumor-associated antigen gene-infected dendritic cells. Hum Immunol 71(3):255–262PubMedGoogle Scholar
  107. 107.
    Melero I, Duarte M, Ruiz J, et al (1999) Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas. Gene Ther 6:1779–1784PubMedGoogle Scholar
  108. 108.
    Zhu M, Terasawa H, Gulley J, et al (2001) Enhanced activation of human T cells via avipox vector-mediated hyperexpression of a triad of costimulatory molecules in human dendritic cells. Cancer Res 61:3725–3734PubMedGoogle Scholar
  109. 109.
    Mazzolini G, Alfaro C, Sangro B, et al (2005) Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas. J Clin Oncol 23:999–1010PubMedGoogle Scholar
  110. 110.
    Fraser JD, Proft T (2008) The bacterial superantigen and superantigen-like proteins. Immunol Rev 225:226–243PubMedGoogle Scholar
  111. 111.
    Si S, Sun Y, Li Z, et al (2006) Gene therapy by membraneexpressed superantigen for alpha-fetoprotein-producing hepatocellular carcinoma. Gene Ther 13:1603–1610PubMedGoogle Scholar
  112. 112.
    Rosenberg SA, Dudley ME (2009) Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol 21:233–240PubMedGoogle Scholar
  113. 113.
    Parkhurst MR, Joo J, Riley JP, et al (2009) Characterization of genetically modified T cell receptors that recognize the CEA:691-699 peptide in the context of HLA-A2.1 on human colorectal cancer cells. Clin Cancer Res 15:169–180PubMedGoogle Scholar
  114. 114.
    Tsuchiyama T, Nakamoto Y, Sakai Y, et al (2008) Optimal amount of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy against hepatocellular carcinoma by M1 macrophage activation. Cancer Sci 99:2075–2082PubMedGoogle Scholar
  115. 115.
    Stefani AL, Barzon L, Castagliuolo I, et al (2005) Systemic efficacy of combined suicide/cytokine gene therapy in a murine model of hepatocellular carcinoma. J Hepatol 42:728–735PubMedGoogle Scholar
  116. 116.
    Tesniere A, Schlemmer F, Boige V, et al (2010) Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 29:482–491PubMedGoogle Scholar
  117. 117.
    Baxevanis CN, Perez SA, Papamichail M (2009) Combinatorial treatments including vaccines, chemotherapy and monoclonal antibodies for cancer therapy. Cancer Immunol Immunother 58:317–324PubMedGoogle Scholar
  118. 118.
    Guo ZS, Thorne SH, Bartlett DL (2008) Oncolytic virotherapy: molecular targets in tumor-selective replication and carrier cellmediated delivery of oncolytic viruses. Biochim Biophys Acta 1785:217–231PubMedGoogle Scholar
  119. 119.
    Russell SJ (2002) RNA viruses as virotherapy agents. Cancer Gene Ther 9:961–966PubMedGoogle Scholar
  120. 120.
    Mullen JT, Tanabe KK (2003) Viral oncolysis for malignant liver tumors. Ann Surg Oncol 10:596–605PubMedGoogle Scholar
  121. 121.
    Rein DT, Breidenbach M, Curiel DT (2006) Current developments in adenovirus-based cancer gene therapy. Future Oncol 2:137–143PubMedGoogle Scholar
  122. 122.
    Ko D, Hawkins L, Yu DC (2005) Development of transcriptionally regulated oncolytic adenoviruses. Oncogene 24:7763–7774PubMedGoogle Scholar
  123. 123.
    Vollmer CM, Ribas A, Butterfield LH, et al (1999) p53 selective and nonselective replication of an E1B-deleted adenovirus in hepatocellular carcinoma. Cancer Res 59:4369–4374PubMedGoogle Scholar
  124. 124.
    Habib N, Salama H, Abd El Latif Abu Median A, et al (2002) Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma. Cancer Gene Ther 9:254–259PubMedGoogle Scholar
  125. 125.
    Takahashi M, Sato T, Sagawa T, et al (2002) E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor. Mol Ther 5:627–634PubMedGoogle Scholar
  126. 126.
    Li Y, Yu DC, Chen Y, et al (2001) A hepatocellular carcinomaspecific adenovirus variant, CV890, eliminates distant human liver tumors in combination with doxorubicin. Cancer Res 61:6428–6436PubMedGoogle Scholar
  127. 127.
    Hsieh JL, Lee CH, Teo ML, et al (2009) Transthyretin-driven oncolytic adenovirus suppresses tumor growth in orthotopic and ascites models of hepatocellular carcinoma. Cancer Sci 100:537–545PubMedGoogle Scholar
  128. 128.
    Chung YS, Miyatake S, Miyamoto A, et al (2006) Oncolytic recombinant herpes simplex virus for treatment of orthotopic liver tumors in nude mice. Int J Oncol 28:793–798PubMedGoogle Scholar
  129. 129.
    Wu L, Huang TG, Meseck M, et al (2008) rVSV(M Delta 51)-M3 is an effective and safe oncolytic virus for cancer therapy. Hum Gene Ther 19:635–647PubMedGoogle Scholar
  130. 130.
    Altomonte J, Wu L, Chen L, et al (2008) Exponential enhancement of oncolytic vesicular stomatitis virus potency by vectormediated suppression of inflammatory responses in vivo. Mol Ther 16:146–153PubMedGoogle Scholar
  131. 131.
    Altomonte J, Marozin S, Schmid RM, et al (2010) Engineered newcastle disease virus as an improved oncolytic agent against hepatocellular carcinoma. Mol Ther 18:275–284PubMedGoogle Scholar
  132. 132.
    Iankov ID, Blechacz B, Liu C, et al (2007) Infected cell carriers: a new strategy for systemic delivery of oncolytic measles viruses in cancer virotherapy. Mol Ther 15:114–122PubMedGoogle Scholar
  133. 133.
    Dembinski JL, Spaeth EL, Fueyo J, et al (2010) Reduction of nontarget infection and systemic toxicity by targeted delivery of conditionally replicating viruses transported in mesenchymal stem cells. Cancer Gene Ther 17(4):289–297PubMedGoogle Scholar
  134. 134.
    Cody JJ, Douglas JT (2009) Armed replicating adenoviruses for cancer virotherapy. Cancer Gene Ther 16:473–488PubMedGoogle Scholar
  135. 135.
    Zhang ZL, Zou WG, Luo CX, et al (2003) An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy. Cell Res 13:481–489PubMedGoogle Scholar
  136. 136.
    Pawlik TM, Nakamura H, Mullen JT, et al (2002) Prodrug bioactivation and oncolysis of diffuse liver metastases by a herpes simplex virus 1 mutant that expresses the CYP2B1 transgene. Cancer 95:1171–1181PubMedGoogle Scholar
  137. 137.
    Ye X, Lu Q, Zhao Y, et al (2005) Conditionally replicative adenovirus vector carrying TRAIL gene for enhanced oncolysis of human hepatocellular carcinoma. Int J Mol Med 16:1179–1184PubMedGoogle Scholar
  138. 138.
    Pan Q, Liu B, Liu J, et al (2008) Synergistic antitumor activity of XIAP-shRNA and TRAIL expressed by oncolytic adenoviruses in experimental HCC. Acta Oncol 47:135–144PubMedGoogle Scholar
  139. 139.
    Shashkova EV, Spencer JF, Wold WS, et al (2007) Targeting interferon-alpha increases antitumor efficacy and reduces hepatotoxicity of E1A-mutated spread-enhanced oncolytic adenovirus. Mol Ther 15:598–607PubMedGoogle Scholar
  140. 140.
    Su C, Peng L, Sham J, et al (2006) Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-gamma gene yields efficient antitumor activity in immunodeficient and immunocompetent mice. Mol Ther 13:918–927PubMedGoogle Scholar
  141. 141.
    Bortolanza S, Bunuales M, Otano I, et al (2009) Treatment of pancreatic cancer with an oncolytic adenovirus expressing interleukin-12 in Syrian hamsters. Mol Ther 17:614–622PubMedGoogle Scholar
  142. 142.
    Zhao L, Gu J, Dong A, et al (2005) Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer. Hum Gene Ther 16:845–858PubMedGoogle Scholar
  143. 143.
    Malhotra S, Kim T, Zager J, et al (2007) Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas. Surgery 141:520–529PubMedGoogle Scholar
  144. 144.
    Kim JH, Oh JY, Park BH, et al (2006) Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF. Mol Ther 14:361–370PubMedGoogle Scholar
  145. 145.
    Fang L, Pu YY, Hu XC, et al (2010) Antiangiogenesis gene armed tumor-targeting adenovirus yields multiple antitumor activities in human HCC xenografts in nude mice. Hepatol Res 40:216–228PubMedGoogle Scholar
  146. 146.
    Jenks N, Myers R, Greiner SM, et al (2010) Safety Studies on Intrahepatic or Intratumoral Injection of Oncolytic Vesicular Stomatitis Virus Expressing Interferon-Beta in Rodents and Nonhuman Primates. Hum Gene Ther 21(4):451–462PubMedGoogle Scholar
  147. 147.
    Blechacz B, Splinter PL, Greiner S, et al (2006) Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma. Hepatology 44:1465–1477PubMedGoogle Scholar
  148. 148.
    Liu TC, Hwang T, Park BH, et al (2008) The targeted oncolytic poxvirus JX-594 demonstrates antitumoral, antivascular, and anti-HBV activities in patients with hepatocellular carcinoma. Mol Ther 16:1637–1642PubMedGoogle Scholar
  149. 149.
    Merrick AE, Ilett EJ, Melcher AA (2009) JX-594, a targeted oncolytic poxvirus for the treatment of cancer. Curr Opin Investig Drugs 10:1372–1382PubMedGoogle Scholar

Copyright information

© Springer Verlag France 2011

Authors and Affiliations

  • G. Gonzalez-Aseguinolaza
    • 1
    • 2
  • J. Prieto
    • 1
    • 3
  • R. Hernandez-Alcoceba
    • 1
    • 2
  1. 1.Division of Gene Therapy and HepatologyCIMAPamplonaSpain
  2. 2.University of Navarra, Foundation for Applied Medical ResearchPamplonaSpain
  3. 3.CIBERehdUniversity Clinic of NavarraPamplonaSpain

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