Oncolytic viruses for the therapy of brain tumors and other solid malignancies: A review

Frontiers in Bioscience

Volumn 8, Issue , 2003, Pages

  Fulci, Giulia ^a   Chiocca, Ennio Antonio ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Cancer; Gene Therapy; Oncolytic Virus; Review; Treatment; Tumors; Virus

Indexed keywords

AD 1118; AD DF3 E1; ANTINEOPLASTIC AGENT; AVE 1A04I; CN 706; CN 787; CV 764; D 115202; D 120; D 1922 947; G 207; G 47 DELTA; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HRR 3; INTERLEUKIN 4; MYB 34 5; MYB34 5; NV 1020; NV 1023; ONYX 015; ONYX 300; ONYX 305; ONYX 320; PV 701; R 3616; R 47 DELTA; R 8305; R 8307; RRP 450; THYMIDINE KINASE; UNCLASSIFIED DRUG;

ADENOVIRUS; BRAIN TUMOR; CLINICAL TRIAL; DNA MODIFICATION; DRUG EFFICACY; GENETIC COMPLEMENTATION; GENETIC ENGINEERING; HERPES SIMPLEX VIRUS; HUMAN; IMMUNE RESPONSE; NEWCASTLE DISEASE PARAMYXOVIRUS; NONHUMAN; ONCOLYTIC VIRUS; PARVOVIRUS; POLIOMYELITIS VIRUS; REOVIRUS; REVIEW; SOLID TUMOR; TISSUE SPECIFICITY; TRANSCRIPTION REGULATION; TREATMENT OUTCOME; VACCINIA VIRUS; VESICULAR STOMATITIS VIRUS; VIRUS MUTATION; VIRUS REPLICATION; WILD TYPE;

ADENOVIRIDAE; NEWCASTLE DISEASE VIRUS; ONYX; PARAMYXOVIRIDAE; PARVOVIRUS; POLIOVIRUS; REOVIRUS SP.; SIMPLEXVIRUS; VACCINIA VIRUS; VESICULAR STOMATITIS VIRUS;

EID: 3142756540     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: None     Document Type: Review

References (154)

1. De Pace, N. G.: Ginecologia 9, 82 (1912)
2. Webb, H. E. & Smith, C. E.: Viruses in the treatment of cancer. Lancet 1, 1206-1208 (1970)
3. Martuza, R. L., Malick, A., Markert, J. M., Ruffner, K. L. & Coen, D. M.: Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 252, 854-856. (1991)
4. Yue, Z. & Shatkin, A. J.: Enzymatic and control functions of reovirus structural proteins. Curr Top Microbiol Immunol 233, 31-56. (1998)
5. Klein, P. A.: Antibody-mediated immunity to transplantable tumors following reovirus oncolysis. Pathol Microbiol 30, 222-245 (1967)
6. Coffey, M. C., Strong, J. E., Forsyth, P. A. & Lee, P. W.: Reovirus therapy of tumors with activated Ras pathway. Science 282, 1332-1334. (1998)
7. Strong, J. E., Coffey, M. C., Tang, D., Sabinin, P. & Lee, P. W.: The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. Embo J 17, 3351-3362. (1998)
8. Bischoff, J. R. & Samuel, C. E.: Mechanism of interferon action. Activation of the human P1/eIF-2 alpha protein kinase by individual reovirus s-class mRNAs: s1 mRNA is a potent activator relative to s4 mRNA. Virology 172, 106-115. (1989)
9. Mundschau, L. J. & Faller, D. V.: Oncogenic ras induces an inhibitor of double-stranded RNA-dependent eukaryotic initiation factor 2 alpha-kinase activation. J Biol Chem 267, 23092-23098. (1992)
10. Galanis, E., Vile, R. & Russell, S. J.: Delivery systems intended for in vivo gene therapy of cancer: targeting and replication competent viral vectors. Crit Rev Oncol Hematol 38, 177-192. (2001)
11. Lorence, R. M., Katubig, B. B., Reichard, K. W., Reyes, H. M., Phuangsab, A., Sassetti, M. D., Walter, R. J. & Peeples, M. E.: Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy. Cancer Res 54, 6017-6021 (1994)
12. Lorence, R. M., Reichard, K. W., Katubig, B. B., Reyes, H. M., Phuangsab, A., Mitchell, B. R., Cascino, C. J., Walter, R. J. & Peeples, M. E.: Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J Natl Cancer Inst 86, 1228-1233 (1994)
13. Schirrmacher, V., Ahlert, T., Probstle, T., Steiner, H. H., Herold-Mende, C., Gerhards, R. & Hagmuller, E.: Immunization with virus-modified tumor cells. Semin Oncol 25, 677-696. (1998)
14. Cassel, W. A., Murray, D. R. & Phillips, H. S.: A phase II study on the postsurgical management of Stage II malignant melanoma with a Newcastle disease virus oncolysate. Cancer 52, 856-860. (1983)
15. Batliwalla, F. M., Bateman, B. A., Serrano, D., Murray, D., Macphail, S., Maino, V. C., Ansel, J. C., Gregersen, P. K. & Armstrong, C. A.: A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire. Mol Med 4, 783-794. (1998)
16. Liebrich, W., Schlag, P., Manasterski, M., Lehner, B., Stohr, M., Moller, P. & Schirrmacher, V.: In vitro and clinical characterisation of a Newcastle disease virus-modified autologous tumour cell vaccine for treatment of colorectal cancer patients. Eur J Cancer 27, 703-710 (1991)
17. Stojdl, D. F., Lichty, B., Knowles, S., Marius, R., Atkins, H., Sonenberg, N. & Bell, J. C.: Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med 6, 821 -825. (2000)
18. Williams, B. R.: PKR; a sentinel kinase for cellular stress. Oncogene 18, 6112-6120. (1999)
19. Stojdl, D. F., Abraham, N., Knowles, S., Marius, R., Brasey, A., Lichty, B. D., Brown, E. G., Sonenberg, N. & Bell, J. C.: The murine double-stranded RNA-dependent protein kinase PKR is required for resistance to vesicular stomatitis virus. J Virol 74, 9580-9585. (2000)
20. Fernandez, M., Porosnicu, M., Markovic, D. & Barber, G. N.: Genetically engineered vesicular stomatitis virus in gene therapy: application for treatment of malignant disease. J Virol 76, 895-904 (2002)
21. Flanagan, E. B., Zamparo, J. M., Ball, L. A., Rodriguez, L. L. & Wertz, G. W.: Rearrangement of the genes of vesicular stomatitis virus eliminates clinical disease in the natural host: new strategy for vaccine development. J Virol 75, 6107-6114 (2001)
22. Mastrangelo, M. J., Eisenlohr, L. C., Gomella, L. & Lattime, E. C.: Poxvirus vectors: orphaned and underappreciated. J Clin Invest 105, 1031-1034. (2000)
23. Moss, B.: Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proc Natl Acad Sci U S A 93, 11341-11348. (1996)
24. McCart, J. A., Ward, J. M., Lee, J., Hu, Y., Alexander, H. R., Libutti, S. K., Moss, B. & Bartlett, D. L.: Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res 61, 8751-8757 (2001)
25. Smith, G. L. & Moss, B.: Infectious poxvirus vectors have capacity for at least 25 000 base pairs of foreign DNA. Gene 25, 21-28. (1983)
26. Puhlmann, M., Gnant, M., Brown, C. K., Alexander, H. R. & Bartlett, D. L.: Thymidine kinase-deleted vaccinia virus expressing purine nucleoside phosphorylase as a vector for tumor-directed gene therapy. Hum Gene Ther 10, 649-657 (1999)
27. Gnant, M. F., Berger, A. C., Huang, J., Puhlmann, M., Wu, P. C., Merino, M. J., Bartlett, D. L., Alexander, H. R., Jr. & Libutti, S. K.: Sensitization of tumor necrosis factor alpha-resistant human melanoma by tumor-specific in vivo transfer of the gene encoding endothelial monocyte-activating polypeptide II using recombinant vaccinia virus. Cancer Res 59, 4668-4674 (1999)
28. Shaughnessy, E., Lu, D., Chatterjee, S. & Wong, K. K.: Parvoviral vectors for the gene therapy of cancer. Semin Oncol 23, 159-171. (1996)
29. Telerman, A., Tuynder, M., Dupressoir, T., Robaye, B., Sigaux, F., Shaulian, E., Oren, M., Rommelaere, J. & Amson, R.: A model for tumor suppression using H-1 parvovirus. Proc Natl Acad Sci U S A 90, 8702-8706. (1993)
30. Moehler, M., Blechacz, B., Weiskopf, N., Zeidler, M., Stremmel, W., Rommelaere, J., Galle, P. R. & Cornelis, J. J.: Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors. Cancer Gene Ther 8, 158-167 (2001)
31. Zhou, Z. H., Chen, D. H., Jakana, J., Rixon, F. J. & Chiu, W.: Visualization of tegument-capsid interactions and DNA in intact herpes simplex virus type 1 virions. J Virol 73, 3210-3218. (1999)
32. Montgomery, R. I., Warner, M. S., Lum, B. J. & Spear, P. G.: Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 87, 427-436. (1996)
33. Geraghty, R. J., Krummenacher, C., Cohen, G. H., Eisenberg, R. J. & Spear, P. G.: Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280, 1618-1620 (1998)
34. Roizman, B.: The function of herpes simplex virus genes: a primer for genetic engineering of novel vectors. Proc Natl Acad Sci U S A 93, 11307-11312. (1996)
35. Jacobs, A., Breakefield, X. O. & Fraefel, C.: HSV-1-based vectors for gene therapy of neurological diseases and brain tumors: part I. HSV-1 structure, replication and pathogenesis. Neoplasia 1, 387-401. (1999)
36. Whitley, R. J., Kimberlin, D. W. & Roizman, B.: Herpes simplex viruses. Clin Infect Dis 26, 541-553; quiz 554-545. (1998)
37. Saeki, Y., Fraefel, C., Ichikawa, T., Breakefield, X. O. & Chiocca, E. A.: Improved helper virus-free packaging system for HSV amplicon vectors using an ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome. Mol Ther 3, 591-601 (2001)
38. Markert, J. M., Medlock, M. D., Rabkin, S. D., Gillespie, G. Y., Todo, T., Hunter, W. D., Palmer, C. A., Feigenbaum, F., Tornatore, C., Tufaro, F. & Martuza, R. L.: Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther 7, 867-874 (2000)
39. Rampling, R., Cruickshank, G., Papanastassiou, V., Nicoll, J., Hadley, D., Brennan, D., Petty, R., MacLean, A., Harland, J., McKie, E., Mabbs, R. & Brown, M.: Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther 7, 859-866 (2000)
40. Louis, N., Fender, P., Barge, A., Kitts, P. & Chroboczek, J.: Cell-binding domain of adenovirus serotype 2 fiber. J Virol 68, 4104-4106. (1994)
41. Henry, L. J., Xia, D., Wilke, M. E., Deisenhofer, J. & Gerard, R. D.: Characterization of the knob domain of the adenovirus type 5 fiber protein expressed in Escherichia coli. J Virol 68, 5239-5246. (1994)
42. Varga, M. J., Weibull, C. & Everitt, E.: Infectious entry pathway of adenovirus type 2. J Virol 65, 6061-6070. (1991)
43. Greber, U. F., Willetts, M., Webster, P. & Helenius, A.: Stepwise dismantling of adenovirus 2 during entry into cells. Cell 75, 477-486. (1993)
44. Norman, K. L., Farassati, F. & Lee, P. W.: Oncolytic viruses and cancer therapy. Cytokine Growth Factor Rev 12, 271-282. (2001)
45. Chakravarti, D., Ogryzko, V., Kao, H. Y., Nash, A., Chen, H., Nakatani, Y. & Evans, R. M.: A viral mechanism for inhibition of p300 and PCAF acetyltransferase activity. Cell 96, 393-403. (1999)
46. Yew, P. R. & Berk, A. J.: Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature 357, 82-85. (1992)
47. White, E., Cipriani, R., Sabbatini, P. & Denton, A.: Adenovirus E1B 19-kilodalton protein overcomes the cytotoxicity of E1A proteins. J Virol 65, 2968-2978 (1991)
48. White, E., Sabbatini, P., Debbas, M., Wold, W. S., Kusher, D. I. & Gooding, L. R.: The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha. Mol Cell Biol 12, 2570-2580 (1992)
49. Tollefson, A. E., Ryerse, J. S., Scaria, A., Hermiston, T. W. & Wold, W. S.: The E3-11.6-kDa adenovirus death protein (ADP) is required for efficient cell death: characterization of cells infected with adp mutants. Virology 220, 152-162. (1996)
50. Hermiston, T. W., Tripp, R. A., Sparer, T., Gooding, L. R. & Wold, W. S.: Deletion mutation analysis of the adenovirus type 2 E3-gp19K protein: identification of sequences within the endoplasmic reticulum lumenal domain that are required for class I antigen binding and protection from adenovirus-specific cytotoxic T lymphocytes. J Virol 67, 5289-5298. (1993)
51. Dimitrov, T., Krajcsi, P., Hermiston, T. W., Tollefson, A. E., Hannink, M. & Wold, W. S.: Adenovirus E3-10.4K/14.5K protein complex inhibits tumor necrosis factor-induced translocation of cytosolic phospholipase A2 to membranes. J Virol 71, 2830-2837. (1997)
52. Smith, R. R., Huebner, R. J., Rowe, P. W., Schatten, W. E. & B., T. L.: Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 9, 1211-1218 (1956)
53. Bischoff, J. R., Kirn, D. H., Williams, A., Heise, C., Horn, S., Muna, M., Ng, L., Nye, J. A., Sampson-Johannes, A., Fattaey, A. & McCormick, F.: An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274, 373-376. (1996)
54. Whyte, P., Ruley, H. E. & Harlow, E.: Two regions of the adenovirus early region IA proteins are required for transformation. J Virol 62, 257-265. (1988)
55. Fueyo, J., Gomez-Manzano, C., Alemany, R., Lee, P. S., McDonnell, T. J., Mitlianga, P., Shi, Y. X., Levin, V. A., Yung, W. K. & Kyritsis, A. P.: A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 19, 2-12 (2000)
56. Heise, C., Hermiston, T., Johnson, L., Brooks, G., Sampson-Johannes, A., Williams, A., Hawkins, L. & Kirn, D.: An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med 6, 1134-1139 (2000)
57. Khuri, F. R., Nemunaitis, J., Ganly, I., Arseneau, J., Tannock, I. F., Romel, L., Gore, M., Ironside, J., MacDougall, R. H., Heise, C., Randlev, B., Gillenwater, A. M., Bruso, P., Kaye, S. B., Hong, W. K. & Kirn, D. H.: 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 6, 879-885 (2000)
58. Kirn, D., Hermiston, T. & McCormick, F.: ONYX-015: clinical data are encouraging. Nat Med 4, 1341-1342 (1998)
59. Gromeier, M., Lachmann, S., Rosenfeld, M. R., Gutin, P. H. & Wimmer, E.: Intergeneric poliovirus recombinants for the treatment of malignant glioma. Proc Natl Acad Sci U S A 97, 6803-6808. (2000)
60. Douglas, J. T., Rogers, B. E., Rosenfeld, M. E., Michael, S. I., Feng, M. & Curiel, D. T.: Targeted gene delivery by tropism-modified adenoviral vectors. Nat Biotechnol 14, 1574-1578. (1996)
61. Miller, C. R., Buchsbaum, D. J., Reynolds, P. N., Douglas, J. T., Gillespie, G. Y., Mayo, M. S., Raben, D. & Curiel, D. T.: Differential susceptibility of primary and established human glioma cells to adenovirus infection: targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer. Cancer Res 58, 5738-5748. (1998)
62. Wickham, T. J., Roelvink, P. W., Brough, D. E. & Kovesdi, I.: Adenovirus targeted to heparan-containing receptors increases its gene delivery efficiency to multiple cell types. Nat Biotechnol 14, 1570-1573. (1996)
63. Laquerre, S., Anderson, D. B., Stolz, D. B. & Glorioso, J. C.: Recombinant herpes simplex virus type 1 engineered for targeted binding to erythropoietin receptor-bearing cells. J Virol 72, 9683-9697. (1998)
64. Hong, J. S. & Engler, J. A.: Domains required for assembly of adenovirus type 2 fiber trimers. J Virol 70, 7071-7078. (1996)
65. Barry, M. A., Dower, W. J. & Johnston, S. A.: Toward cell-targeting gene therapy vectors: selection of cell-binding peptides from random peptide-presenting phage libraries. Nat Med 2, 299-305. (1996)
66. Goldstein, D. J. & Weller, S. K.: Factor (s) present in herpes simplex virus type 1-infected cells can compensate for the loss of the large subunit of the viral ribonucleotide reductase: characterization of an ICP6 deletion mutant. Virology 166, 41-51 (1988)
67. Mineta, T., Rabkin, S. D. & Martuza, R. L.: Treatment of malignant gliomas using ganciclovir-hypersensitive, ribonucleotide reductase-deficient herpes simplex viral mutant. Cancer Res 54, 3963-3966. (1994)
68. Yoon, S. S., Nakamura, H., Carroll, N. M., Bode, B. P., Chiocca, E. A. & Tanabe, K. K.: An oncolytic herpes simplex virus type 1 selectively destroys diffuse liver metastases from colon carcinoma. Faseb J 14, 301-311. (2000)
69. Boviatsis, E. J., Park, J. S., Sena-Esteves, M., Kramm, C. M., Chase, M., Efird, J. T., Wei, M. X., Breakefield, X. O. & Chiocca, E. A.: Long-term survival of rats harboring brain neoplasms treated with ganciclovir and a herpes simplex virus vector that retains an intact thymidine kinase gene. Cancer Res 54, 5745-5751. (1994)
70. Andreansky, S. S., He, B., Gillespie, G. Y., Soroceanu, L., Markert, J., Chou, J., Roizman, B. & Whitley, R. J.: The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. Proc Natl Acad Sci U S A 93, 11313-11318. (1996)
71. Chou, J., Kern, E. R., Whitley, R. J. & Roizman, B.: Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science 250, 1262-1266. (1990)
72. He, B., Gross, M. & Roizman, B.: The gamma (1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci U S A 94, 843-848. (1997)
73. Clemens, M. J. & Elia, A.: The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine Res 17, 503-524. (1997)
74. Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J. & Saltiel, A. R.: A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci U S A 92, 7686-7689. (1995)
75. Gibbs, J. B., Graham, S. L., Hartman, G. D., Koblan, K. S., Kohl, N. E., Omer, C. A. & Oliff, A.: Farnesyltransferase inhibitors versus Ras inhibitors. Curr Opin Chem Biol 1, 197-203. (1997)
76. Mineta, T., Rabkin, S. D., Yazaki, T., Hunter, W. D. & Martuza, R. L.: Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nat Med 1, 938-943. (1995)
77. Kooby, D. A., Carew, J. F., Halterman, M. W., Mack, J. E., Bertino, J. R., Blumgart, L. H., Federoff, H. J. & Fong, Y.: Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207) Faseb J 13, 1325-1334. (1999)
78. Coukos, G., Makrigiannakis, A., Kang, E. H., Caparelli, D., Benjamin, I., Kaiser, L. R., Rubin, S. C., Albelda, S. M. & Molnar-Kimber, K. L.: Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer. Clin Cancer Res 5, 1523-1537. (1999)
79. Toda, M., Rabkin, S. D. & Martuza, R. L.: Treatment of human breast cancer in a brain metastatic model by G207, a replication-competent multimutated herpes simplex virus 1. Hum Gene Ther 9, 2177-2185. (1998)
80. Walker, J. R., McGeagh, K. G., Sundaresan, P., Jorgensen, T. J., Rabkin, S. D. & Martuza, R. L.: Local and systemic therapy of human prostate adenocarcinoma with the conditionally replicating herpes simplex virus vector G207. Hum Gene Ther 10, 2237-2243. (1999)
81. Chahlavi, A., Todo, T., Martuza, R. L. & Rabkin, S. D.: Replication-competent herpes simplex virus vector G207 and cisplatin combination therapy for head and neck squamous cell carcinoma. Neoplasia 1, 162-169. (1999)
82. Randazzo, B. P., Bhat, M. G., Kesari, S., Fraser, N. W. & Brown, S. M.: Treatment of experimental subcutaneous human melanoma with a replication-restricted herpes simplex virus mutant. J Invest Dermatol 108, 933-937. (1997)
83. Oyama, M., Ohigashi, T., Hoshi, M., Nakashima, J., Tachibana, M., Murai, M., Uyemura, K. & Yazaki, T.: Intravesical and intravenous therapy of human bladder cancer by the herpes vector G207. Hum Gene Ther 11, 1683-1693. (2000)
84. Barker, D. D. & Berk, A. J.: Adenovirus proteins from both E1B reading frames are required for transformation of rodent cells by viral infection and DNA transfection. Virology 156, 107-121. (1987)
85. Fulci, G., Ishii, N. & Van Meir, E. G.: p53 and brain tumors: from gene mutations to gene therapy. Brain Pathol 8,599-613. (1998)
86. Fulci, G. & Van Meir, E. G.: p53 and the CNS: tumors and developmental abnormalities. Mol Neurobiol 19, 61-77. (1999)
87. Heise, C., Sampson-Johannes, A., Williams, A., McCormick, F., Von Hoff, D. D. & Kirn, D. H.: ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 3, 639-645. (1997)
88. Rogulski, K. R., Freytag, S. O., Zhang, K., Gilbert, J. D., Paielli, D. L., Kim, J. H., Heise, C. C. & Kirn, D. H.: In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy. Cancer Res 60, 1193-1196. (2000)
89. Hall, A. R., Dix, B. R., O'Carroll, S. J. & Braithwaite, A. W.: p53-dependent cell death/apoptosis is required for a productive adenovirus infection. Nat Med 4, 1068-1072. (1998)
90. Rothmann, T., Hengstermann, A., Whitaker, N. J., Scheffner, M. & zur Hausen, H.: Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells. J Virol 72, 9470-9478. (1998)
91. Goodrum, F. D. & Ornelles, D. A.: p53 status does not determine outcome of E1B 55-kilodalton mutant adenovirus lytic infection. J Virol 72, 9479-9490. (1998)
92. Turnell, A. S., Grand, R. J. & Gallimore, P. H.: The replicative capacities of large E1B-null group A and group C adenoviruses are independent of host cell p53 status. J Virol 73, 2074-2083. (1999)
93. Kratzer, F., Rosorius, O., Heger, P., Hirschmann, N., Dobner, T., Hauber, J. & Stauber, R. H.: The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2. Oncogene 19, 850-857. (2000)
94. McCormick, F.: ONYX-015 selectivity and the p14ARF pathway. Oncogene 19, 6670-6672 (2000)
95. Fulci, G., Labuhn, M., Maier, D., Lachat, Y., Hausmann, O., Hegi, M. E., Janzer, R. C., Merlo, A. & Van Meir, E. G.: p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive events in human glioblastoma. Oncogene 19, 3816-3822. (2000)
96. Ramachandra, M., Rahman, A., Zou, A., Vaillancourt, M., Howe, J. A., Antelman, D., Sugarman, B., Demers, G. W., Engler, H., Johnson, D. & Shabram, P.: Re-engineering adenovirus regulatory pathways to enhance oncolytic specificity and efficacy. Nat Biotechnol 19, 1035-1041. (2001)
97. Sherr, C. J.: The Pezcoller lecture: cancer cell cycles revisited. Cancer Res 60, 3689-3695. (2000)
98. Miyatake, S., Iyer, A., Martuza, R. L. & Rabkin, S. D.: Transcriptional targeting of herpes simplex virus for cell-specific replication. J Virol 71, 5124-5132. (1997)
99. Sacks, W. R., Greene, C. C., Aschman, D. P. & Schaffer, P. A.: Herpes simplex virus type 1 ICP27 is an essential regulatory protein. J Virol 55, 796-805. (1985)
100. DeLuca, N. A., McCarthy, A. M. & Schaffer, P. A.: Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J Virol 56, 558-570. (1985)
101. Tilghman, S. M. & Belayew, A.: Transcriptional control of the murine albumin/alpha-fetoprotein locus during development. Proc Natl Acad Sci U S A 79, 5254-5257. (1982)
102. Chung, R. Y., Saeki, Y. & Chiocca, E. A.: B-myb promoter retargeting of herpes simplex virus gamma34.5 gene-mediated virulence toward tumor and cycling cells. J Virol 73, 7556-7564 (1999)
103. Nakamura, H., Kasuya, H., Mullen, J. T., Yoon, S. S., Pawlik, T. M., Chandrasekhar, S., Donahue, J. M., Chiocca, E. A., Chung, R. Y. & Tanabe, K. K.: Regulation of herpes simplex virus gamma (1)34.5 expression and oncolysis of diffuse liver metastases by Myb34.5. J Clin Invest 109, 871-882 (2002)
104. Hallenbeck, P. L., Chang, Y. N., Hay, C., Golightly, D., Stewart, D., Lin, J., Phipps, S. & Chiang, Y. L.: A novel tumor-specific replication-restricted adenoviral vector for gene therapy of hepatocellular carcinoma. Hum Gene Ther 10, 1721-1733. (1999)
105. Camper, S. A. & Tilghman, S. M.: The activation and silencing of gene transcription in the liver. Biotechnology 16, 81-87 (1991)
106. Rodriguez, R., Schuur, E. R., Lim, H. Y., Henderson, G. A., Simons, J. W. & Henderson, D. R.: Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res 57, 2559-2563. (1997)
107. Kurihara, T., Brough, D. E., Kovesdi, I. & Kufe, D. W.: Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen. J Clin Invest 106, 763-771. (2000)
108. Kufe, D., Inghirami, G., Abe, M., Hayes, D., Justi-Wheeler, H. & Schlom, J.: Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma 3, 223-232. (1984)
109. Friedman, E. L., Hayes, D. F. & Kufe, D. W.: Reactivity of monoclonal antibody DF3 with a high molecular weight antigen expressed in human ovarian carcinomas. Cancer Res 46, 5189-5194. (1986)
110. Yu, D. C., Sakamoto, G. T. & Henderson, D. R.: Identification of the transcriptional regulatory sequences of human kallikrein 2 and their use in the construction of calydon virus 764, an attenuated replication competent adenovirus for prostate cancer therapy. Cancer Res 59, 1498-1504. (1999)
111. Yu, D. C., Chen, Y., Seng, M., Dilley, J. & Henderson, D. R.: The addition of adenovirus type 5 region E3 enables calydon virus 787 to eliminate distant prostate tumor xenografts. Cancer Res 59, 4200-4203 (1999)
112. Smith, E. R. & Chiocca, E. A.: Oncolytic viruses as novel anticancer agents: turning one scourge against another. Expert Opin Investig Drugs 9, 311 -327. (2000)
113. Wildner, O., Blaese, R. M. & Morris, J. C.: Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of herpes simplex virus-thymidine kinase. Cancer Res 59, 410-413 (1999)
114. Wildner, O. & Morris, J. C.: The role of the E1B 55 kDa gene product in oncolytic adenoviral vectors expressing herpes simplex virus-tk: assessment of antitumor efficacy and toxicity. Cancer Res 60, 4167-4174 (2000)
115. Carroll, N. M., Chase, M., Chiocca, E. A. & Tanabe, K. K.: The effect of ganciclovir on herpes simplex virus-mediated oncolysis. J Surg Res 69, 413-417 (1997)
116. Lambright, E. S., Amin, K., Wiewrodt, R., Force, S. D., Lanuti, M., Propert, K. J., Litzky, L., Kaiser, L. R. & Albelda, S. M.: Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy. Gene Ther 8, 946-953 (2001)
117. Aghi, M., Chou, T. C., Suling, K., Breakefield, X. O. & Chiocca, E. A.: Multimodal cancer treatment mediated by a replicating oncolytic virus that delivers the oxazaphosphorine/rat cytochrome P450 2B1 and ganciclovir/herpes simplex virus thymidine kinase gene therapies. Cancer Res 59, 3861-3865 (1999)
118. Chase, M., Chung, R. Y. & Chiocca, E. A.: An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy. Nat Biotechnol 16, 444-448 (1998)
119. Ikeda, K., Ichikawa, T., Wakimoto, H., Silver, J. S., Deisboeck, T. S., Finkelstein, D., Harsh, G. R., Louis, D. N., Bartus, R. T., Hochberg, F. H. & Chiocca, E. A.: Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses. Nat Med 5, 881-887. (1999)
120. Freytag, S. O., Rogulski, K. R., Paielli, D. L., Gilbert, J. D. & Kim, J. H.: A novel three-pronged approach to kill cancer cells selectively: concomitant viral, double suicide gene, and radiotherapy. Hum Gene Ther 9, 1323-1333 (1998)
121. Post, D. E. & Van Meir, E. G.: Generation of bidirectional hypoxia/HIF-responsive expression vectors to target gene expression to hypoxic cells. Gene Ther 8, 1801-1807 (2001)
122. Sauthoff, H., Heitner, S., Rom, W. N. & Hay, J. G.: Deletion of the adenoviral E1b-19kD gene enhances tumor cell killing of a replicating adenoviral vector. Hum Gene Ther 11, 379-388 (2000)
123. Harrison, D., Sauthoff, H., Heitner, S., Jagirdar, J., Rom, W. N. & Hay, J. G.: Wild-type adenovirus decreases tumor xenograft growth, but despite viral persistence complete tumor responses are rarely achieved - deletion of the viral E1b-19-kD gene increases the viral oncolytic effect. Hum Gene Ther 12, 1323-1332 (2001)
124. Hawkins, L. K. & Hermiston, T.: Gene delivery from the E3 region of replicating human adenovirus: evaluation of theE3B region. Gene Ther 8, 1142-1148 (2001)
125. Hawkins, L. K. & Hermiston, T. W.: Gene delivery from the E3 region of replicating human adenovirus: evaluation of the ADP region. Gene Ther 8, 1132-1141 (2001)
126. Hawkins, L. K., Johnson, L., Bauzon, M., Nye, J. A., Castro, D., Kitzes, G. A., Young, M. D., Holt, J. K., Trown, P. & Hermiston, T. W.: Gene delivery from the E3 region of replicating human adenovirus: evaluation of the 6.7 K/gp19 K region. Gene Ther 8, 1123-1131 (2001)
127. Bennett, J. J., Malhotra, S., Wong, R. J., Delman, K., Zager, J., St-Louis, M., Johnson, P. & Fong, Y.: Interleukin 12 secretion enhances antitumor efficacy of oncolytic herpes simplex viral therapy for colorectal cancer. Ann Surg 233, 819-826 (2001)
128. Andreansky, S., He, B., van Cott, J., McGhee, J., Markert, J. M., Gillespie, G. Y., Roizman, B. & Whitley, R. J.: Treatment of intracranial gliomas in immunocompetent mice using herpes simplex viruses that express murine interleukins. Gene Ther 5, 121-130 (1998)
129. Todo, T., Martuza, R. L., Rabkin, S. D. & Johnson, P. A.: Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc Natl Acad Sci U S A 98, 6396-6401 (2001)
130. Jennings, S. R., Rice, P. L., Kloszewski, E. D., Anderson, R. W., Thompson, D. L. & Tevethia, S. S.: Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells. J Virol 56, 757-766 (1985)
131. Hill, A. B., Barnett, B. C., McMichael, A. J. & McGeoch, D. J.: HLA class I molecules are not transported to the cell surface in cells infected with herpes simplex virus types 1 and 2. J Immunol 152, 2736-2741 (1994)
132. York, I. A., Roop, C., Andrews, D. W., Riddell, S. R., Graham, F. L. & Johnson, D. C.: A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77, 525-535 (1994)
133. Hill, A., Jugovic, P., York, I., Russ, G., Bennink, J., Yewdell, J., Ploegh, H. & Johnson, D.: Herpes simplex virus turns off the TAP to evade host immunity. Nature 375, 411-415 (1995)
134. Fruh, K., Ahn, K., Djaballah, H., Sempe, P., van Endert, P. M., Tampe, R., Peterson, P. A. & Yang, Y.: A viral inhibitor of peptide transporters for antigen presentation. Nature 375, 415-418 (1995)
135. Zhang, J. F., Hu, C., Geng, Y., Selm, J., Klein, S. B., Orazi, A. & Taylor, M. W.: Treatment of a human breast cancer xenograft with an adenovirus vector containing an interferon gene results in rapid regression due to viral oncolysis and gene therapy. Proc Natl Acad Sci U S A 93, 4513-4518 (1996)
136. Mastrangelo, M. J., Maguire, H. C., Jr., Eisenlohr, L. C., Laughlin, C. E., Monken, C. E., McCue, P. A., Kovatich, A. J. & Lattime, E. C.: Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther 6, 409-422. (1999)
137. Raj, K., Ogston, P. & Beard, P.: Virus-mediated killing of cells that lack p53 activity. Nature 412, 914-917 (2001)
138. Kirn, D., Martuza, R. L. & Zwiebel, J.: Replication-selective virotherapy for cancer: Biological principles, risk management and future directions. Nat Med 7, 781-787. (2001)
139. Kirn, D.: Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned? Gene Ther 8, 89-98 (2001)
140. Nemunaitis, J., Cunningham, C., Buchanan, A., Blackburn, A., Edelman, G., Maples, P., Netto, G., Tong, A., Randlev, B., Olson, S. & Kirn, D.: Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity. Gene Ther 8, 746-759 (2001)
141. Muldoon, L. L., Nilaver, G., Kroll, R. A., Pagel, M. A., Breakefield, X. O., Chiocca, E. A., Davidson, B. L., Weissleder, R. & Neuwelt, E. A.: Comparison of intracerebral inoculation and osmotic blood-brain barrier disruption for delivery of adenovirus, herpesvirus, and iron oxide particles to normal rat brain. Am J Pathol 147, 1840-1851 (1995)
142. Muldoon, L. L., Pagel, M. A., Kroll, R. A., Roman-Goldstein, S., Jones, R. S. & Neuwelt, E. A.: A physiological barrier distal to the anatomic blood-brain barrier in a model of transvascular delivery. AJNR Am J Neuroradiol 20, 217-222 (1999)
143. Kramm, C. M., Rainov, N. G., Sena-Esteves, M., Barnett, F. H., Chase, M., Herrlinger, U., Pechan, P. A., Chiocca, E. A. & Breakefield, X. O.: Long-term survival in a rodent model of disseminated brain tumors by combined intrathecal delivery of herpes vectors and ganciclovir treatment. Hum Gene Ther 7, 1989-1994 (1996)
144. Kramm, C. M., Rainov, N. G., Sena-Esteves, M., Chase, M., Pechan, P. A., Chiocca, E. A. & Breakefield, X. O.: Herpes vector-mediated delivery of marker genes to disseminated central nervous system tumors. Hum Gene Ther 7, 291-300 (1996)
145. Conry, R. M., Khazaeli, M. B., Salen, M. N., Allen, K. O., Barlow, D. L., Moore, S. E., Craig, D., Arani, R. B., Schlom, J. & LoBuglio, A. F.: Phase I trial of a recombinant vaccinia virus encoding carcinoembryonic antigen in metastatic adenocarcinoma: comparison of intradermal versus subcutaneous administration. Clin Cancer Res 5, 2330-2337 (1999)
146. Eder, J. P., Kantoff, P. W., Roper, K., Xu, G. X., Bubley, G. J., Boyden, J., Gritz, L., Mazzara, G., Oh, W. K., Arlen, P., Tsang, K. Y., Panicali, D., Schlom, J. & Kufe, D. W.: A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer. Clin Cancer Res 6, 1632-1638 (2000)
147. Mukherjee, S., Haenel, T., Himbeck, R., Scott, B., Ramshaw, I., Lake, R. A., Harnett, G., Phillips, P., Morey, S., Smith, D., Davidson, J. A., Musk, A. W. & Robinson, B.: Replication-restricted vaccinia as a cytokine gene therapy vector in cancer: persistent transgene expression despite antibody generation. Cancer Gene Ther 7, 663-670. (2000)
148. Stohrer, M., Boucher, Y., Stangassinger, M. & Jain, R. K.: Oncotic pressure in solid tumors is elevated. Cancer Res 60, 4251-4255 (2000)
149. Hampl, M., Tanaka, T., Albert, P. S., Lee, J., Ferrari, N. & Fine, H. A.: Therapeutic effects of viral vector-mediated antiangiogenic gene transfer
150. Zinkernagel, R. M.: Immunology taught by viruses. Science 271, 173-178. (1996)
151. Ploegh, H. L.: Viral strategies of immune evasion. Science 280, 248-253. (1998)
152. Ikeda, K., Wakimoto, H., Ichikawa, T., Jhung, S., Hochberg, F. H., Louis, D. N. & Chiocca, E. A.: Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant. J Virol 74, 4765-4775. (2000)
153. Wakimoto, H., Ikeda, K., Abe, T., Ichikawa, T., Hochberg, F. H., Ezekowitz, R. A., Pasternack, M. S. & Chiocca, E. A.: The complement response against an oncolytic virus is species-specific in its activation pathways. Mol Ther 5, 275-282. (2002)
154. Wodarz, D.: Viruses as antitumor weapons: defining conditions for tumor remission. Cancer Res 61, 3501-3507. (2001)