Cervantes-García D; Ortiz-López R; Mayek-Pérez N; Rojas-Martínez A

Language: Spanish
References: 118
Page: 34-45
PDF size: 1667.31 Kb.

Text Extraction

Current oncolytic virotherapy strategies are based in the accumulated understanding of the common molecular mechanisms displayed during cell transformation and viral infection, like cell cycle and apoptosis deregulations. Oncolytic virotherapy aims to achieve a strong cytolytic effect, highly restricted to transformed cells. Here, we describe the oncolytic virotherapy defined as the use of viruses like antitumor agents (wild and gene-modified oncolytic viruses) and the developed strategies to increase antitumor efficacy and safety. In addition, we discuss the advances and challenges concerning the use virotherapy in animal models and clinical trials. Some clinical trials of virotherapy have demonstrated promising results, particularly when combined with standard antineoplastic therapies. These preliminary accomplishments are opening the field for more research in several aspects, like vector modifications, pharmacodynamics, biosafety, new clinical applications, etc.

REFERENCES

1. Wadhwa PD, Zielske SP, Roth JC, Ballas CB, Bowman JE, Gerson SL. Cancer Gene Therapy: Scientific Basis. Annu Rev Med 2002; 53: 427-452.

2. Everts B, van der Poel HG. Replication-selective oncolytic viruses in the treatment of cancer. Cancer Gene Ther 2005; 12(2): 141-161.

3. Stanford MM, Barrett JW, Nazarian SH, Werden S, McFadden G. Oncolytic virotherapy synergism with signaling inhibitors: Rapamycin increases myxoma virus tropism for human tumor cells. J Virol 2007; 81(3): 1251-1260.

4. Lun X, Yang W, Alain T, Shi ZQ, Muzik H, Barret JW, McFadden G, Bell J, Hamilton MG, Senger DL, Forsyth PA. Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. Cancer Res 2005; 65(21): 9982-9990.

5. Donofrio G, Caviran S, van Santen V, Flammini CF. Potential secondary pathogenic role for bovine herpesvirus 4. J Clin Microbiol 2005; 43(7): 3421-3426.

6. Gillet L, Dewals B, Farnir F, de Leval L, Vanderplasschen A. Bovine herpesvirus 4 induces apoptosis of human carcinoma cell lines in vitro and in vivo. Cancer Res 2005; 65(20): 9463-9472.

7. Norman KL, Hirasawa K, Yang AD, Shields MA, Lee PW. Reovirus oncolysis: the Ras/RalGEF/p38 pathway dictates host cell permissiveness to reovirus infection. Proc Natl Acad Sci 2004; 101(30): 11099-11104.

8. Marcato P, Schmulevitz M, Lee PW. Connecting reovirus oncolysis and Ras signaling. Cell Cicle 2005; 4(4): 556-559.

9. Hirasawa K, Nishikawa SG, Norman KL, Coffey MC, Thompson BG, Yoon CS, Waisman DM, Lee PW. Systemic reovirus therapy of metastatic cancer in immune-competent mice. Cancer Res 2003: 63(2): 348-353.

10. Etoh T, Himeno Y, Matsumoto T, Aramaki M, Kawano K, Nishizono A, Kitano S. Oncolytic viral therapy for human pancreatic cancer cells by reovirus. Clin Cancer Res 2003; 9(3): 1218-1223.

11. Phuangsab A, Lorence RM, Reichard KW, Peeples ME, Walter RJ. Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration. Cancer Lett 2001; 172(1): 27-36.

12. Mullen JT, Tanabe KK. Viral oncolysis. Oncologist 2002; 7(2): 106-119.

13. Reichard KW, Lorence RM, Cascino CJ, Peeples MF, Walter RJ, Fernando MB, Reyes HM, Greager JA. Newcastle disease virus selectively kills human tumor cells. J Surg Res 1992; 55(5): 448-453.

14. Lorence RM, Katubig BB, Reichard KW, Reyes HM, Phuangsab A, Sassetti MD, Walter RJ, Peeples MF. Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy. Cancer Res 1994; 54(23): 6017-6021.

15. Elankumaran S, Rockemann D, Samal SK. Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death. J Virol 2006; 80(15): 7522-7534.

16. Shafren DR, Dorahy DJ, Ingham RA, Burns GF, Barry RD. Coxsackievirus A21 binds to decay-accelerating factor but requires intercellular adhesion molecule 1 for cell entry. J Virol 1997; 71(6): 4736-4743.

17. Shafren DR, Au GG, Nguyen T, Newcombe NG, Haley ES, Beagley L, Johansson ES, Hersey P, Barry RD. Systemic therapy of malignant human melanoma tumors by a common cold-producing enterovirus, Coxsackievirus A21. Clin Cancer Res 2004; 10(1): 53-60.

18. Letchworth GJ, Rodriguez LL, Del cbarrera J. Vesicular stomatitis. Vet J 1999; 157(3): 239-60.

19. Barber GN. Vesicular stomatitis virus as an oncolytic vector. Viral Immunol 2004; 17(4):516-527.

20. Balachandran S, Porosnicu M, Barber GN. Oncolytic activity of vesicular stomatitis virus is effective against tumors exhibiting aberrant p53, Ras, or myc function and involves the induction of apoptosis. J Virol 2001; 75(7): 3474-3479.

21. Connor JH, Naczki C, Koumenis C, Lyles DS. Replication and cytopathic effect of oncolytic vesicular stomatitis virus in hypoxic tumor cells in vitro and in vivo. J Virol 2004; 78(17): 8960-8970.

22. Balachandran S, Barber GN. Defective translational control facilitates vesicular stomatitis virus oncolysis. Cancer Cell 2004; 5(1): 51-65.

23. Connor JH, Lyles DS. Inhibition of host and viral translation during vesicular stomatitis virus infection. eIF2 is responsible for the inhibition of viral but not host translation. Biol Chem 2005; 280(14): 13512-13519.

24. Russell SJ. RNA viruses as virotherapy agents. Cancer Gene Ther 2002; 9(12): 961-6.

25. Shinozaki K, Ebert O, Kournioti C, Tai YS, Woo SLC. Oncolysis of Multifocal Hepatocellular carcinoma in the rat liver by hepatic artery infusion of vesicular stomatitis virus. Mol Ther 2004; 9(3): 368-376.

26. Brandenburger A, Legendre D, Avalosse B, Rommelaere J. NS-1 and NS-2 proteins may act synergistically in the cytopathogenicity of parvovirus MVMp. Virology 1990; 174(2): 576-584.

27. Di Piazza M, Mader C, Geletneky K, Herrero y Calle M, Weber E, Schlehofer J, Deleu L, Rommelaere J. Cytosolic activation of cathepsins mediates parvovirus H-1-induced killing of cisplatin and TRAIL-resistant glioma cells. J Virol 2007; 81(8): 4186-4198.

28. Herrero y Calle M, Cornelis JJ, Herold-Mende C, Rommelaere J, Schlehofer JR, Geletneky K. Parvovirus H-1 infection of human glioma cells leads to complete viral replication and efficient cell killing. Int J Cancer 2004; 109(1): 76-84.29. Geletneky K, Herrero y Calle M, Rommelaere J, Schlehofer JR. Oncolytic potential of rodent parvoviruses for cancer therapy in humans: a brief review. J Vet Med 2005; 52(7-8): 327-330.

29. Smith RR, Huebner RJ, Rowe WP, Schatten WE, Thomas LB. Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 1956; 9(6): 1211-1218.

30. Ludlow JW, Skuse GR. Viral oncoprotein binding to pRb, p107, p130, and p300. Virus Res 1995; 35(2): 113-121.

31. Green,NK, Seymour LW. Adenoviral vectors: Systemic delivery and tumor targeting. Cancer Gene Ther 2002; 9(12): 1036-1042.

32. Jones NC. Transformation by the human adenoviruses. Semin Cancer Biol 1990; 1(6): 425-435.

33. Dahiya A, Gavin MR, Luo RX, Dean DC. Role of the LXCXE binding site in Rb function. Mol Cell Biol 2000; 20(18): 6799-6805.

34. Alevizopoulos K, Sanchez B, Amati B. Conserved region 2 of adenovirus E1A has function distinct from pRb binding required to prevent cell cycle arrest by p16INK4 or p27Kip1. Oncogene 2000; 19(16): 2067-2074.

35. Wienzek S, Roth J, Dobbelstein M. E1B 55-kilodaltons oncoproteins of adenovirus types 5 and 12 inactivate and relocalize p53, but not p51 or p73, and cooperate with E4orf6 proteins to destabilize p53. J Virol 2000; 74(1): 193-202.

36. Zhao LY, Liao D. Sequestration of p53 in the cytoplasm by adenovirus type 12 E1B 55-kilodalton oncoprotein is required for inhibition of p53-mediated apoptosis. J Virol 2003; 77(24): 13171-13181.

37. Hickman ES, Moroni MC, Helin K. The role of p53 and pRb in apoptosis and cancer. Curr Opin Genet Dev 2002; 12(1): 60-66.

38. Liu TC, Kirn D. Viruses with deletions in antiapoptotic genes as potential oncolytic agents. Oncogene 2005; 24(40): 6069-6079.

39. Berk AJ. Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus. Oncogene 2005; 24(52): 7673-7685.

40. Robson T, Hirst DG. Transcriptional targeting in cancer gene therapy. J Biomed Biotechnol 2003; (2): 110-137.

41. Sadeghi H, Hitt MM. Transcriptionally targeted adenovirus vectors. Curr Gene Ther 2005; 5(4): 411-427.

42. Kanerva A, Hemminki A. Modified adenovirus for cancer gene therapy. Int J Cancer 2004; 110(4): 475-480.

43. Post DE, Khuri FR, Simons JW, Van Meir EG. Replicative oncolytic adenoviruses in multimodal cancer regimens. Hum Gene Ther 2003; 14(10): 933-946.

44. Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A, McCormick F. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 1996; 274(5286): 373-376.

45. Kirn D. Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): results of phase I and II trials. Expert Opin Biol Ther 2001; 1(3): 525-538.

46. Fueyo J, Gomez-Manzano C, Alemany R, Lee PS, McDonnell TJ, Mitlianga P, Shi YX, Levin VA, Yung WKA, Kyritsis AP. A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 2000; 19(1): 2-12.

47. Gomez-Manzano C, Balague C, Alemany R, Lemoine MG, Mitlianga P, Jiang H, Khan A, Alonso M, Lang FF, Conrad CA, Liu TJ, Bekele N, Yung WKA, Fueyo J. A novel E1A-E1B mutant adenovirus induces glioma regression in vivo. Oncogene 2004; 23(10): 1821-1828.

48. Heise C, Hermiston T, Johnson L, Brooks G, Sampson-Johannes A, Williams A, Hawkins L, Kirn D. 2000. An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med 2000; 6(10): 1134-1139.

49. Cascallo M, Capellà G, Mazo A, Alemany R. Ras-dependent oncolysis with an adenovirus VAI mutant. Cancer Res 2003; 63(17): 5544-5550.

50. Harrington KJ, Linardakis E, Vile RG. Transcriptional control: an essential component of cancer gene therapy strategies? Adv Drug Deliv Rev 2000; 44(2-3): 167-184.

51. Rodriguez R, Schuur ER, Lim HY, Henderson GA, Simons JW, Henderson DR. Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res 1997; 57(13): 2559-2563.

52. Huang TG, Savontaus MJ, Shinozaki K, Sauter BV, Woo SLC. Telomerase-dependent oncolytic adenovirus for cancer treatment. Gene Ther 2003; 10(15): 1241-1247.

53. Lee CT, Park KH, Yanagisawa K, Adachi Y, Ohm JE, Nadaf S, Dikov MM, Curiel DT, Carbone DP. Combination therapy with conditionally replicating adenovirus and replication defective adenovirus. Cancer Res 2004; 64(18): 6660-6665.

54. Li Y, Chen Y, Dilley J, Arroyo T, Ko D, Working P, Yu DC. Carcinoembrionic antigen-producing cell-specific oncolytic adenovirus, OV798, for colorectal cancer therapy. Mol Cancer Ther 2003; 2(10): 1003-1009.

55. Hallenbeck PL, Chang YN, Hay C, Golightly D, Stewart D, Lin J, Phipps S, Chiang YL. A novel tumor-specific replication-restricted adenoviral vector for gene therapy of hepatocellular carcinoma. Hum Gene Ther 1999; 10(10): 1721-1733.

56. Delgado-Enciso I, Cervantes-Garcia D, Martinez-Davila IA, Ortiz-Lopez R, Alemany-Bonastre R, Silva-Platas CI, Lugo-Trampe A, Barrera-Saldaña HA, Galvan-Salazar HR, Coronel-Tene CG, Sanchez-Santillan CF, Rojas-Martinez A. A potent replicative delta-24 adenoviral vector driven by the promoter of human papillomavirus 16 that is highly selective for associated neoplasms. J Gene Med 2007; 9: 852-861.

57. Douglas JT, Kim M, Sumerel LA, Carey DE, Curiel DT. Efficient Oncolysis by a replicating adenovirus (Ad) in vivo is critically dependent on tumor expression of primary Ad receptors. Cancer Res 2001; 61(3): 813-817.

58. Excoffon KJ, Traver GL, Zabner J. The role of the extracellular domain in the biology of the coxsackievirus and adenovirus receptor. Am J Respir Cell Mol Biol 2005; 32(6): 498-503.

59. McConnel MJ, Imperiale MJ. Biology of adenovirus and its use as a vector for gene therapy. Hum Gene Ther 2004; 15(11): 1022-1033.

60. Volk AL, Rivera AA, Kanerva A, Bauerschmitz G, Dmitriev I, Nettelbeck DM, Curiel DT. Enhanced adenovirus infection of melanoma cells by fiber-modification: incorporation of RGD peptide or Ad5/3 chimerism. Cancer Biol Ther 2003; 2(5): 511-515.

61. Martin TA, Watkins G, Jiang WG. The Coxsackie-adenovirus receptor has elevated expression in human breast cancer. Clin Exp Med 2005; 5(3):122-128.

62. Matsumoto K, Shariat SF, Ayala GE, Rauen KA, Lerner SP. Loss of coxsackie and adenovirus receptor expression is associated with features of aggressive bladder cancer. Urology 2005; 66(2): 441-446.

63. Anders M, Christian C, McMahon M, McCormick F, Korn WM. Inhibition of the Raf/MEK/ERK pathway up-regulates expression of the coxsackievirus and adenovirus receptor in cancer cells. Cancer Res 2003; 63(9): 2088-2095.

64. Suzuki K, Fueyo J, Krasnykh V, Reynolds PN, Curiel DT, Alemany R. A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res 2001; 7(1): 120-6.

65. Campbell M, Qu S, Wells S, Sugandha H, Jensen RA. An adenoviral vector containing an arg-gly-asp (RGD) motif in the fiber knob enhances protein product levels from transgenes refractory to expression. Cancer Gene Ther 2003; 10(7): 559-570.

66. Dehari H, Ito Y, Nakamura T, Kobune M, Sasaki K, Yonekura N, Kohama G, Hamad H. Enhanced antitumor effect of RGD fiber-modified adenovirus for gene therapy of oral cancer. Cancer Gene Ther 2003; 10(1): 75-85.

67. Liu Y, Ye T, Sun D, Maynard J, Deisseroth A. Conditionally replication-competent adenoviral vectors with enhanced infectivity for use in gene therapy of melanoma. Hum Gene Ther 2004; 15(7): 637-647.

68. Taki M, Kagawa S, Nishizaki M, Mizuguchi H, Hayakawa T, Kyo S, Nagai K, Urata Y, Tanaka N, Fujiwara T. Enhanced oncolysis by a tropism-modified telomerase-specific replication-selective adenoviral agent OBP-405 (‘Telomelysin-RGD’). Oncogene 2005; 24(19): 3130-3140.

69. Denby L, Work LM, Graham D, Hsu C, von Seggern DJ, Nicklin SA, Baker AH. Adenoviral serotype 5 vectors pseudotyped with fibers from subgroup D show modified tropism in vitro and in vivo. Hum Gene Ther 2004; 15(11): 1054-1064.

70. Krasnykh VN, Mikheeva GV, Douglas JT, Curiel DT. Generation of recombinant adenovirus vectors modified fibers for altering viral tropism. J Virol 1996; 70(10): 6839-6846.

71. Parker AL, Waddington SN, Nicol CG, Shayakhmetov DM, Buckley SM, Denby L, Kemball-Cook G, Ni S, Lieber A, McVey JH, Nicklin SA, Baker AH. Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes. Blood 2006; 108(8): 2554-2561.

72. Parker AL, McVey JH, Doctor JH, Lopez-Franco O, Waddington SN, Havenga MJ, Nicklin SA, Baker AH. Influence of coagulation factor zymogens on the infectivity of adenoviruses pseudotyped with fibers from subgroup D. J Virol 2007; 181(7): 3627-3631.

73. Baker AH, Mcvey JH, Waddington SN, Di Paolo NC, Shayakhmetov DM. The influence of blood on in vivo Adenovirus Bio-distribution and transduction. Mol Ther 2007; 15(8): 1410-1416.

74. Douglas JT, Rogers BE, Rosenfeld ME, Michael SI, Feng M, Curiel DT. Targeted gene delivery by tropism-modified adenoviral vectors. Nat Biotechnol 1996; 14(11): 1574-1578.

75. Ranki T, Kanerva A, Ristimaki A, Hakkarainen T, Sarkioja M, Kangasniemi L, Raki M, Laakkonen P, Goodison S, Hemminki A. A heparan sulfate-targeted conditionally replicative adenovirus, Ad5.pk7-Delta24, for the treatment of advanced breast cancer. Gene Ther 2007; 14(1): 58-67.

76. Zhang Q, Nie M, Sham J, Su C, Xue H, Chua D, Wang W, Cui Z, Liu Y, Liu C, Jiang M, Fang G, Liu X, Wu M, Qian Q. Effective gene-viral therapy for telomerase-positive cancers by selective replicative-competent adenovirus combining with endostatin gene. Cancer Res 2004; 64(15): 5390-5397.

77. Heideman DA, Steenbergen RD, van der Torre J, Scheffner M, Alemany R, Gerritsen WR, Meijer CM, Snijders PJF, van Beusechem VW. Oncolytic adenovirus expressing a p53 variant resistant to degradation by HPV E6 protein exhibits potent and selective replicative in cervical cancer. Mol Ther 2005; 12(6): 1083-1090.

78. Ren XW, Liang M, Meng X, Ma H, Zhao Y, Guo J, Cai N, Chen HZ, Ye SL, Hu F. A tumor-specific conditionally replicative adenovirus vector expressing TRAIL for gene therapy of hepatocellular carcinoma. Cancer Gene Ther 2006; 13(2): 159-168.

79. Guo W, Zhu H, Zhang L, Davis J, Teraishi F, Roth JA, Stephens C, Fueyo J, Jiang H, Conrad C, Fang B. Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models. Cancer Gene Ther 2006; 13(1): 82-90.

80. Zhang ZL, Zou WG, Luo CX, Li BH, Wang JH, Sun LY, Qian QJ, Liu XY. An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy. Cell Res 2003; 113(6): 481-489.

81. Oosterhoff D, Pinedo HM, Witlox MA, Carette JE, Gerritsen WR, van Beusechem VW. Gene-directed enzyme prodrug therapy with carboxylesterase enhances the anticancer efficacy of the conditionally replicating adenovirus AdD24. Gene Ther 2005; 12(12): 1011-1018.

82. Heise C, Lemmon M, Kirn D. 2000. Efficacy with a replication-selective adenovirus plus cisplatin-based chemotherapy: dependence on sequencing but not p53 functional status or route of administration. Clin Cancer Res 2000; 6(12): 4908-4914.

83. Dilley J, Reddy S, Ko D, Nguyen N, Rojas G, Working P, Yu DC. Oncolytic adenovirus CG7870 in combination with radiation demonstrates synergistic enhancements of antitumor efficacy without loss of specificity. Cancer Gene Ther 2005; 12(8): 715-722.

84. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007; 132(7): 2557-2576.

85. Méndez-Sánchez N, Zamora-Valdés D, Vásquez-Fernández F, Uribe M. Hepatocellular carcinoma in Hispanics. Ann Hepatol 2007; 6(4): 279-280.

86. Shinozaki K, Ebert O, Woo SL. Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV. Hepatology 2005; 41(1): 196-203.

87. Blechacz B, Splinter PL, Greiner S, Myers R, Peng KW, Federspiel MJ, Russell SJ, LaRusso NF. Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma. Hepatology 2006; 44(6): 1465-1477.

88. Su CQ, Wang XH, Chen J, Liu YJ, Wang WG, Li LF, Wu MC, Qian QJ. Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma. World J Gastroenterol 2006; 12(47): 7613-7620.

89. Zhang Q, Chen G, Peng L, Wang X, Yang Y, Liu C, Shi W, Su C, Wu H, Liu X, Wu M, Qian Q. Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus. Clin Cancer Res 2006; 12(21): 6523-6531.

90. Wirth T, Kühnel F, Fleischmann-Mundt B, Woller N, Djojosubroto M, Lenhard RK, Manns M, Zender L, Kubicka S. Telomerase-dependent virotherapy overcomes resistance of hepatocellular carcinomas against chemotherapy and tumor necrosis factor-related apoptosis-inducing ligand by elimination of Mcl-1. Cancer Res 2005; 65(16): 7393-7402.

91. Prince GA, Porter DD, Jenson AB, Horswood RL, Chanock RM, Ginsberg HS. Pathogenesis of adenovirus type 5 pneumonia in cotton rats (Sigmodon hispidus). J Virol 1993; 67(1):101-111

92. Rojas-Martinez A, Wyde PR, Montgomery CA, Chen SH, Woo SL, Aguilar-Cordova E. Distribution, persistency, toxicity, and lack of replication of an E1A-deficient adenoviral vector after intracardiac delivery in the cotton rat. Cancer Gene Ther 1998; 5(6): 365-370.

93. Toth K, Spencer JF, Tollefson AE, Kuppuswamy M, Doronin K, Lichtenstein DL, La Regina MC, Prince GA, Wold WS. Cotton rat tumor model for the evaluation of oncolytic adenoviruses. Hum Gene Ther 2005; 16(1): 139-146.

94. Eichelberger MC. The cotton rat as a model to study influenza pathogenesis and immunity. Viral Immunol 2007; 20(2): 243-249.

95. Ottolini MG, Blanco JC, Eichelberger MC, Porter DD, Pletneva L, Richardson JY, Prince GA. The cotton rat provides a useful small-animal model for the study of influenza virus pathogenesis. J Gen Virol 2005; 86(Pt 10): 2823-2830.

96. Zhao X, Liu E, Chen FP, Sullender WM. In vitro and in vivo fitness of respiratory syncytial virus monoclonal antibody escape mutants. J Virol 2006; 80(23): 11651-11657.

97. Yim KC, Carroll CJ, Tuyama A, Cheshenko N, Carlucci MJ, Porter DD, Prince GA, Herold BC. The cotton rat provides a novel model to study genital herpes infection and to evaluate preventive strategies. J Virol 2005; 79(23): 14632-14639.

98. Williams JV, Tollefson SJ, Johnson JE, Crowe JE. The cotton rat (Sigmodon hispidus) is a permissive small animal model of human metapneumovirus infection, pathogenesis, and protective immunity. J Virol 2005; 79(17): 10944-10951.

99. Rytik PG, Kutcherov II, Muller WE, Poleschuk NN, Duboiskaya GP, Kruzo M, Podolskaya IA. Small animal model of HIV-1 infection. J Clin Virol 2004; Suppl 1: S83-S87.

100. Elwood RL, Wilson S, Blanco JC, Yim K, Pletneva L, Nikoneko B, Samala R, Joshi R, Hemming VG, Trucksis M. The American cotton rat: a novel model for pulmonary tuberculosis. Tuberculosis (Edinb) 2007; 87(2): 145-154.

101. Mahler M, Heidtmann W, Niewiesk S, Gruber A, Fossmark R, Beil W, Hedrich H, Wagner S. Experimental Helicobacter pylori infection induces antral-predominant, chronic active gastritis in hispid cotton rats (Sigmodon hispidus). Helicobacter 2005; 10(4): 332-344.

102. Steel JC, Morrison BJ, Mannan P, Abu-Asab MS, Wildner O, Miles BK, Yim KC, Ramanan V, Prince GA, Morris JC. Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus. Virology 2007; 369(1):131-142.

103. Clyde WA. Experimental models for study of common respiratory viruses. Environ Health Perspect 1980; 35: 107-112.

104. Kunstyr I, Maess J, Naumann S, Kaup FJ, Kraft V, Knocke KW. Adenovirus pneumonia in guineapigs: an experimental reproduction of the disease. Lab Anim 18(1): 55-60.

105. Jogler C, Hoffman D, Theegarten D, Grunwald T, Uberla K, Wildner O. Replication properties of human adenovirus in vivo and in cultures of primary cells from different animal species. J Virol 2006; 80(7): 3549-3558.

106. Thomas MA, Spencer JF, La Regina MC, Dhar D, Tollefson AE, Toth K, Wold WS. Syrian hamster as a permissive immunocompetent animal model for the study of oncolytic adenovirus vectors. Cancer Res 2006; 66(3): 1270-1276.

107. Hara H, Kobayashi A, Yoshida K, Ohashi M, Ohnami S, Uchida E, Higashihara E, Yoshida T, Aoki K. Local interferon-alpha gene therapy elicits systemic immunity in a syngeneic pancreatic cancer model in hamster. Cancer Sci 2007; 98(3):455-463.

108. Stoeckel J, Hay JG. Drug evaluation: Reolysin—wild-type reovirus as a cancer therapeutic. Curr Opin Mol Ther 2006; 8(3): 249-260.

109. Pecora AL, Rizvi N, Cohen GI, Meropol NJ, Sterman D, Marshall JL, Golderg S, Gross P, O’Neil JD, Groene WS, Roberts MS, Rabin H, Bamat MK, Lorence RM. Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol 2002; 20(9): 2220-2222.

110. Ganly I, Kirn D, Eckhardt G, Rodriguez GI, Soutar DS, Otto R, Robertson AG, Park O, Gulley ML, Heise C, Von Hoff DD, Kaye SB. A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res 2000; 6(3): 798-806.

111. Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L, Gore M, Ironside J, MacDougall RH, Heise C, Randlev B, Gillenmater AM, Bruso P, Kaye SB, Hong WK, Kirn DH. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 2000; 6(8): 879-885.

112. Reid T, Galanis E, Abbruzzese J, Sze D, Wein LM, Andrews J, Randlev B, Heise C, Uprichard M, Hatfield M, Rome L, Rubin J, Kirn D. Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints. Cancer Res 2002; 62(21): 6070-6079.

113. Nemunaitis J, Khuri F, Ganly I, Arseneau J, Posner M, Vokes E, Kuhn J, McCarty T, Landers S, Blackburn A, Romel L, Randlev B, Kaye S, Kirn D. Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J Clin Oncol 2001; 19(2): 289-298.

114. Lu W, Zheng S, Li XF, Huang JJ, Zheng X, Li Z. Intra-tumor injection of H101, a recombinant adenovirus, in combination with chemotherapy in patients with advanced cancers: a pilot phase II clinical trial. World J Gastroenterol 2004; 10(24): 3634-3638.

115. Small EJ, Carducci MA, Burke JM, Rodriguez R, Fong L, van Ummersen L, Yu DC, Aimi J, Ando D, Working P, Kirn D, Wilding G. A phase I trial of intravenous CG7870, a replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic prostate cancer. Mol Ther 2006; 14(1): 107-117.

116. DeWeese TL, van der Poel H, Li S, Mikhak B, Drew R, Goemann M, Hamper U, DeJong R, Detorie N, Rodriguez R, Haulk T, DeMarzo AM, Piantadosi S, Yu DC, Chen Y, Henderson DR, Carducci MA, Nelson WG, Simons JW. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res 2001; 61(20): 7464-7472.

117. Demers GW, Johnson DE, Tsai V, Wen SF, Quijano E, Machemer T, Philopena J, Ramachandra M, Howe JA, Shabram P, Ralston R, Engler H. 2003. Pharmacologic indicators of antitumor efficacy for oncolytic virotherapy. Cancer Res 2003; 63(14): 4003-4008.

118. Aghi M, Martuza RL. Oncolytic viral therapies – the clinical experience. Oncogene 2005; 24(52): 7802-7816.