Clinical trials have indicated that oncolytic viruses might be developed as safe and effective anticancer agents.
The translation of oncolytic viruses from the culture dish to preclinical tumour models to studies involving patients has revealed new hurdles to cancer therapy that can be overcome using multidisciplinary approaches.
Novel strategies can be used to facilitate viral evasion of the immune system, the prevention of viral uptake by the liver, and an increased specificity for tumour cells, either at the cell surface or through intracellular restriction.
Oncolytic viruses can be engineered to target the same genetic mutations that provide tumour cells with a proliferative or survival advantage in patients.
The intravenous delivery of viruses must be perfected if oncolytic virus-based therapeutics are to be used to treat patients with metastatic tumours.
In the past 5 years, the field of oncolytic virus research has matured significantly and is moving past the stage of being a laboratory novelty into a new era of preclinical and clinical trials. What have recent anticancer trials of oncolytic viruses taught us about this exciting new line of therapeutics?
De Pace, N. G. Sulla scomparsa di un enorme cancro vegetante del callo dell'utero senza cura chirurgica. Ginecologia 9, 82–88 (1912).
Dock, G. Rabies virus vaccination in a patient with cervical carcinoma. Amer. J. Med. Sci. b127 (1904).
Viral Therapy of Human Cancers (eds Sinkovics, J. G & Horvath, J. C.) (Taylor and Francis CRC, Baco Raton, 2004).
Benencia, F. et al. HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer. Mol. Ther. 12, 789–802 (2005) (10.1016/j.ymthe.2005.03.026).
Xia, Z. J. et al. Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus. Ai Zheng 23, 1666–1670 (2004).
Shah, A. C., Benos, D., Gillespie, G. Y. & Markert, J. M. Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas. J. Neurooncol. 65, 203–226 (2003).
Kaufman, H. L. et al. Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. J. Clin. Invest. 115, 1903–1912 (2005).
Chiocca, E. A. et al. A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol. Ther. 10, 958–966 (2004).
Harrow, S. et al. HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival. Gene Ther. 11, 1648–1658 (2004).
Markert, J. M. et al. 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).
Khuri, F. R. et al. 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. Nature Med. 6, 879–885 (2000).
Heise, C. et al. ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nature Med. 3, 639–645 (1997).
O'Shea, C. C., Soria, C., Bagus, B. & McCormick, F. Heat shock phenocopies E1B-55K late functions and selectively sensitizes refractory tumor cells to ONYX-015 oncolytic viral therapy. Cancer Cell 8, 61–74 (2005).
Reid, T., Warren, R. & Kirn, D. Intravascular adenoviral agents in cancer patients: lessons from clinical trials. Cancer Gene Ther. 9, 979–986 (2002). This review describes some of the unique properties that are associated with oncolytic virus therapy.
Lorence, R. M. et al. Overview of phase I studies of intravenous administration of PV701, an oncolytic virus. Curr. Opin. Mol. Ther. 5, 618–624 (2003).
Pecora, A. L. et al. Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J. Clin. Oncol. 20, 2251–2266 (2002).
Lorence, R. M. et al. Continuing the interaction between non-clinical and clinical studies. Third International Meeting on Oncolytic Virus Therapeutics: Banff, Alberta (12 Mar 2005).
Reid, T. et al. Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: a phase I trial. Gene Ther. 8, 1618–1626 (2001).
Taneja, S., MacGregor, J., Markus, S., Ha, S. & Mohr, I. Enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cells. Proc. Natl Acad. Sci. USA 98, 8804–8808 (2001).
Naniche, D. et al. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J. Virol. 67, 6025–6032 (1993).
Dorig, R. E., Marcil, A., Chopra, A. & Richardson, C. D. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75, 295–305 (1993).
Hsu, E. C., Iorio, C., Sarangi, F., Khine, A. A. & Richardson, C. D. CDw150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the munosuppressive properties of this virus. Virology 279, 9–21 (2001).
Tatsuo, H., Ono, N., Tanaka, K. & Yanagi, Y. The cellular receptor for measles virus: SLAM (CDw150). Uirusu 50, 289–296 (in Japanese) (2000).
Schneider, U., Bullough, F., Vongpunsawad, S., Russell, S. J. & Cattaneo, R. Recombinant measles viruses efficiently entering cells through targeted receptors. J. Virol. 74, 9928–9936 (2000).
Hammond, A. L. et al. Single-chain antibody displayed on a recombinant measles virus confers entry through the tumor-associated carcinoembryonic antigen. J. Virol. 75, 2087–2096 (2001).
Bucheit, A. D. et al. An oncolytic measles virus engineered to enter cells through the CD20 antigen. Mol. Ther. 7, 62–72 (2003).
Peng, K. W. et al. Oncolytic measles viruses displaying a single-chain antibody against CD38, a myeloma cell marker. Blood 101, 2557–2562 (2003).
Hahm, B. et al. Measles virus infects and suppresses proliferation of T lymphocytes from transgenic mice bearing human signaling lymphocytic activation molecule. J. Virol. 77, 3505–3515 (2003).
Vongpunsawad, S., Oezgun, N., Braun, W. & Cattaneo, R. Selectively receptor-blind measles viruses: identification of residues necessary for SLAM- or CD46-induced fusion and their localization on a new hemagglutinin structural model. J. Virol. 78, 302–313 (2004).
Nakamura, T. et al. Antibody-targeted cell fusion. Nature Biotechnol. 22, 331–336 (2004).
Russell, S. Retargeting, attachment and entry of oncolytic viruses. American Society of Gene Therapy Meeting: St. Louis (2005).
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). Description of a transcriptionally regulated adenovirus for the treatment of patients with prostate cancer.
O'Shea, C. C. et al. Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity. Cancer Cell 6, 611–623 (2004). Clarification of the mechanism of action of the Onyx-015 virus.
Bergelson, J. M. et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275, 1320–1323 (1997).
Douglas, J. T. et al. Targeted gene delivery by tropism-modified adenoviral vectors. Nature Biotechnol. 14, 1574–1578 (1996).
Shayakhmetov, D. M., Li, Z. Y., Ni, S. & Lieber, A. Analysis of adenovirus sequestration in the liver, transduction of hepatic cells, and innate toxicity after injection of fiber-modified vectors. J. Virol. 78, 5368–5381 (2004).
Kawakami, Y. et al. Substitution of the adenovirus serotype 5 knob with a serotype 3 knob enhances multiple steps in virus replication. Cancer Res. 63, 1262–1269 (2003).
Breidenbach, M. et al. Genetic replacement of the adenovirus shaft fiber reduces liver tropism in ovarian cancer gene therapy. Hum. Gene Ther. 15, 509–518 (2004).
Nilsson, M. et al. Development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells. J. Gene Med. 6, 631–641 (2004).
Dmitriev, I. et al. An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J. Virol. 72, 9706–9713 (1998).
Borovjagin, A. V. et al. Complex mosaicism is a novel approach to infectivity enhancement of adenovirus type 5-based vectors. Cancer Gene Ther. 12, 475–486 (2005).
Maisner, A. et al. Recombinant measles virus requiring an exogenous protease for activation of infectivity. J. Gen. Virol. 81, 441–449 (2000).
Cattaneo, R. Defining tropism of oncolytic vectors by protease availability: measles viruses selectively fusing matrix-metalloproteinase expressing cells. Third International Meeting on Oncolytic Virus Therapeutics: Banff, Alberta (12 Mar 2005).
Alain, T. et al. Oncolysis by reovirus intermediate subviral particles. Third International Meeting on Oncolytic Virus Therapeutics: Banff, Alberta (12 Mar 2005).
Van Themsche, C., Potworowski, E. F. & St. Pierre, Y. Stromelysin-1 (MMP-3) is inducible in T lymphoma cells and accelerates the growth of lymphoid tumors in vivo. Biochem. Biophys. Res. Commun. 315, 884–891 (2004).
Au, G. G., Lindberg, A. M., Barry, R. D. & Shafren, D. R. Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21. Int. J. Oncol. 26, 1471–1476 (2005). Characterization of the oncolytic activity of coxsackievirus.
Shafren, D. R., Sylvester, D., Johansson, E. S., Campbell, I. G. & Barry, R. D. Oncolysis of human ovarian cancers by echovirus type 1. Int. J. Cancer 115, 320–328 (2005).
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. USA 97, 6803–6808 (2000). First description of a poliovirus as an oncolytic virus.
Gromeier, M. et al. The human poliovirus receptor. Receptor-virus interaction and parameters of disease specificity. Ann. NY Acad. Sci. 753, 19–36 (1995).
Ochiai, H. et al. Treatment of intracerebral neoplasia and neoplastic meningitis with regional delivery of oncolytic recombinant poliovirus. Clin. Cancer Res. 10, 4831–4838 (2004).
Nakamura, T. et al. Rescue and propagation of fully retargeted oncolytic measles viruses. Nature Biotechnol. 23, 209–214 (2005). Describes a unique approach that could be used to target many different kinds of enveloped viruses. The first description of a replication competent re-targeted virus that is not compromised in its ability to grow to high titres.
Peng, K. W. Measles virus imaging and tumour targeting. Third International Meeting on Oncolytic Virus Therapeutics: Banff, Alberta (12 Mar 2005).
Ohno, S., Ono, N., Takeda, M., Takeuchi, K. & Yanagi, Y. Dissection of measles virus V protein in relation to its ability to block α/β interferon signal transduction. J. Gen. Virol. 85, 2991–2999 (2004).
Sana, T. R., Janatpour, M. J., Sathe, M., McEvoy, L. M. & McClanahan, T. K. Microarray analysis of primary endothelial cells challenged with different inflammatory and immune cytokines. Cytokine 29, 256–269 (2005).
Chawla-Sarkar, M. et al. Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis 8, 237–249 (2003).
de Veer, M. J. et al. Functional classification of interferon-stimulated genes identified using microarrays. J. Leukoc. Biol. 69, 912–920 (2001).
Khabar, K. S. et al. Expressed gene clusters associated with cellular sensitivity and resistance towards anti-viral and anti-proliferative actions of interferon. J. Mol. Biol. 342, 833–846 (2004).
Dunn, G. P. et al. A critical function for type I interferons in cancer immunoediting. Nature Immunol. 6, 722–729 (2005).
Ikeda, H., Old, L. J. & Schreiber, R. D. The roles of IFN γ in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 13, 95–109 (2002). A very nice review of the data supporting the idea that immunosurveillance is an important factor in tumour evolution.
Stojdl, D. F. et al. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nature Med. 7, 821–825 (2000).
Stojdl, D. F. et al. VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell 4, 263–275 (2003).
Faria, P. A. et al. VSV disrupts the Rae1/mrnp41 mRNA nuclear export pathway. Mol. Cell 17, 93–102 (2005).
Wang, F. et al. Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier. Nature Immunol. 5, 1266–1274 (2004). First description of how the tropism of the myxoma poxvirus is regulated by components of the innate antiviral response.
Ahmed, M., Cramer, S. D. & Lyles, D. S. Sensitivity of prostate tumors to wild type and M protein mutant vesicular stomatitis viruses. Virology 330, 34–49 (2004).
Shinozaki, K., Ebert, O. & Woo, S. L. Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV. Hepatology 41, 196–203 (2005).
Balachandran, S., Porosnicu, M. & Barber, G. N. 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. 75, 3474–3479 (2001).
Park, M. S., Garcia-Sastre, A., Cros, J. F., Basler, C. F. & Palese, P. Newcastle disease virus V protein is a determinant of host range restriction. J. Virol. 77, 9522–9532 (2003).
Muster, T. et al. Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants. Int. J. Cancer 110, 15–21 (2004).
Bjornsti, M. A. & Houghton, P. J. Lost in translation: dysregulation of cap-dependent translation and cancer. Cancer Cell 5, 519–523 (2004). A brief but excellent review of the importance of translation regulation and cancer.
Huang, S. & Houghton, P. J. Targeting mTOR signaling for cancer therapy. Curr. Opin. Pharmacol. 3, 371–377 (2003).
Perkins, D. J. & Barber, G. N. Defects in translational regulation mediated by the α subunit of eukaryotic initiation factor 2 inhibit antiviral activity and facilitate the malignant transformation of human fibroblasts. Mol. Cell. Biol. 24, 2025–2040 (2004).
Topisirovic, I. et al. Eukaryotic translation initiation factor 4E activity is modulated by HOXA9 at multiple levels. Mol. Cell. Biol. 25, 1100–1112 (2005).
Clemens, M. J. Targets and mechanisms for the regulation of translation in malignant transformation. Oncogene 23, 3180–3188 (2004).
Kaempfer, R. RNA sensors: novel regulators of gene expression. EMBO Rep. 4, 1043–1047 (2003).
Mulvey, M., Poppers, J., Sternberg, D. & Mohr, I. Regulation of eIF2α phosphorylation by different functions that act during discrete phases in the herpes simplex virus type 1 life cycle. J. Virol. 77, 10917–10928 (2003).
Rivas-Estilla, A. M. et al. PKR-dependent mechanisms of gene expression from a subgenomic hepatitis C virus clone. J. Virol. 76, 10637–10653 (2002).
Farassati, F., Yang, A. D. & Lee, P. W. Oncogenes in Ras signalling pathway dictate host-cell permissiveness to herpes simplex virus 1. Nature Cell Biol. 3, 745–750 (2001).
Balachandran, S. & Barber, G. N. Defective translational control facilitates vesicular stomatitis virus oncolysis. Cancer Cell 5, 51–65 (2004). First report of the ability of an oncolytic virus to exploit tumour cell defects in the regulation of translation.
Langland, J. O. & Jacobs, B. L. Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains of E3L. Virology 324, 419–429 (2004).
Gerotto, M. et al. Two PKR inhibitor HCV proteins correlate with early but not sustained response to interferon. Gastroenterology 119, 1649–1655 (2000).
He, B., Gross, M. & Roizman, B. The γ134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α 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. USA 94, 843–848 (1997).
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. Nature Med. 1, 938–943 (1995).
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).
Mashour, G. A. et al. Therapeutic efficacy of G207 in a novel peripheral nerve sheath tumor model. Exp. Neurol. 169, 64–71 (2001).
Sundaresan, P., Hunter, W. D., Martuza, R. L. & Rabkin, S. D. Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation in mice. J. Virol. 74, 3832–3841 (2000).
Toda, M., Rabkin, S. D., Kojima, H. & Martuza, R. L. Herpes simplex virus as an in situ cancer vaccine for the induction of specific anti-tumor immunity. Hum. Gene Ther. 10, 385–393 (1999).
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). First description of an engineered, replicating virus for oncolytic therapy.
Takaoka, A. et al. Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence. Nature 424, 516–523 (2003).
Munoz-Fontela, C. et al. Resistance to viral infection of super p53 mice. Oncogene 24, 3059–3062 (2005).
Balachandran, S. & Barber, G. N. Vesicular stomatitis virus (VSV) therapy of tumors. IUBMB Life 50, 135–138 (2000).
Lee, C. J., Liao, C. L. & Lin, Y. L. Flavivirus activates phosphatidylinositol 3-kinase signaling to block caspase-dependent apoptotic cell death at the early stage of virus infection. J. Virol. 79, 8388–8399 (2005).
Reboredo, M., Greaves, R. F. & Hahn, G. Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication. J. Gen. Virol. 85, 3555–3567 (2004).
Wright, C. W., Means, J. C., Penabaz, T. & Clem, R. J. The baculovirus anti-apoptotic protein Op-IAP does not inhibit drosophila caspases or apoptosis in drosophila S2 cells and instead sensitizes S2 cells to virus-induced apoptosis. Virology 335, 61–71 (2005).
Liu, T. C. et al. An E1B-19 kDa gene deletion mutant adenovirus demonstrates tumor necrosis factor-enhanced cancer selectivity and enhanced oncolytic potency. Mol. Ther. 9, 786–803 (2004).
Shelton, J. G. et al. The epidermal growth factor receptor gene family as a target for therapeutic intervention in numerous cancers: what's genetics got to do with it? Expert Opin. Ther. Targets 9, 1009–1030 (2005).
McCart, J. A. et al. Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res. 61, 8751–8757 (2001).
Garcia, M. A., Guerra, S., Gil, J., Jimenez, V. & Esteban, M. Anti-apoptotic and oncogenic properties of the dsRNA-binding protein of vaccinia virus, E3L. Oncogene 21, 8379–8387 (2002).
Bessis, N., GarciaCozar, F. J. & Boissier, M. C. Immune responses to gene therapy vectors: influence on vector function and effector mechanisms. Gene Ther. 11 (suppl.), S10–S17 (2004).
Hirasawa, K. et al. Systemic reovirus therapy of metastatic cancer in immune-competent mice. Cancer Res. 63, 348–353 (2003).
Thorne, S. The design and testing of oncolytic vaccinia virus vectors for efficient systemic delivery of transgenes. Third International Meeting on Oncolytic Virus Therapeutics: Banff, Alberta (11 Mar 2005).
Ichihashi, Y. Extracellular enveloped vaccinia virus escapes neutralization. Virology 217, 478–485 (1996).
Law, M. & Smith, G. L. Antibody neutralization of the extracellular enveloped form of vaccinia virus. Virology 280, 132–142 (2001).
Fisher, K. D. et al. Polymer-coated adenovirus permits efficient retargeting and evades neutralising antibodies. Gene Ther. 8, 341–348 (2001).
Green, N. K. et al. Extended plasma circulation time and decreased toxicity of polymer-coated adenovirus. Gene Ther. 11, 1256–1263 (2004). Identifies many of the problems that viral therapeutics face, and novel delivery approaches to overcome these hurdles.
Seymour, L. Systemic delivery of adenovirus: use of polymers to mask unwanted infection and enable intravenous delivery. Third International Meeting on Oncolytic Virus Therapeutics: Banff, Alberta (10 Mar 2005).
Ikeda, K. et al. Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses. Nature Med. 5, 881–887 (1999).
Ilan, Y. et al. Transient immunosuppression with FK506 permits long-term expression of therapeutic genes introduced into the liver using recombinant adenoviruses in the rat. Hepatology 26, 949–956 (1997).
Jooss, K., Yang, Y. & Wilson, J. M. Cyclophosphamide diminishes inflammation and prolongs transgene expression following delivery of adenoviral vectors to mouse liver and lung. Hum. Gene Ther. 7, 1555–1566 (1996).
Kuriyama, S. et al. Transient cyclophosphamide treatment before intraportal readministration of an adenoviral vector can induce re-expression of the original gene construct in rat liver. Gene Ther. 6, 749–757 (1999).
Smith, T. A., White, B. D., Gardner, J. M., Kaleko, M. & McClelland, A. Transient immunosuppression permits successful repetitive intravenous administration of an adenovirus vector. Gene Ther. 3, 496–502 (1996).
Endo, T. et al. In situ cancer vaccination with a replication-conditional HSV for the treatment of liver metastasis of colon cancer. Cancer Gene Ther. 9, 142–148 (2002).
Toda, M., Iizuka, Y., Kawase, T., Uyemura, K. & Kawakami, Y. Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV. Cancer Gene Ther. 9, 356–364 (2002).
Hummel, J. L., Safroneeva, E. & Mossman K. L. The role of ICP0-null HSV-1 and interferon signaling defects in the effective treatment of breast adenocarcinoma. Mol. Ther. 31 Aug 2005 (10.1016/j.ymthe.2005.07.533).
Bergman, I. Re-targeting VSV: a candidate cancer therapeutic. Third International Meeting on Oncolytic Virus Therapeutics: Banff, Alberta (12 Mar 2005).
Breitbach, C. Investigation of the oncolytic activity of vesicular stomatitis virus in murine cancer models. Third International Meeting on Oncolytic Virus Therapeutics: Banff, Alberta (11 Mar 2005).
Newcombe, N. G. et al. Cellular receptor interactions of C-cluster human group A coxsackieviruses. J. Gen. Virol. 84, 3041–3050 (2003).
He, Y. et al. Complexes of poliovirus serotypes with their common cellular receptor, CD155. J. Virol. 77, 4827–4835 (2003).
Anderson, B. D., Nakamura, T., Russell, S. J. & Peng, K. W. High CD46 receptor density determines preferential killing of tumor cells by oncolytic measles virus. Cancer Res. 64, 4919–4926 (2004).
Lin, R., Noyce, R. S., Collins, S. E., Everett, R. D. & Mossman, K. L. The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes. J. Virol. 78, 1675–1684 (2004).
Norman, K. L., Hirasawa, K., Yang, A. D., Shields, M. A. & Lee, P. W. Reovirus oncolysis: the Ras–RalGEF–p38 pathway dictates host cell permissiveness to reovirus infection. Proc. Natl Acad. Sci. USA 101, 11099–11104 (2004).
Stone, D. et al. Development and assessment of human adenovirus type 11 as a gene transfer vector. J. Virol. 79, 5090–5104 (2005).
Holterman, L. et al. Novel replication-incompetent vector derived from adenovirus type 11 (Ad11) for vaccination and gene therapy: low seroprevalence and non-cross-reactivity with Ad5. J. Virol. 78, 13207–13215 (2004).
Fukuhara, H. et al. Improvement of transduction efficiency of recombinant adenovirus vector conjugated with cationic liposome for human oral squamous cell carcinoma cell lines. Oral Oncol. 39, 601–609 (2003).
Eto, Y. et al. PEGylated adenovirus vectors containing RGD peptides on the tip of PEG show high transduction efficiency and antibody evasion ability. J. Gene Med. 7, 604–612 (2005).
Croyle, M. A., Chirmule, N., Zhang, Y. & Wilson, J. M. “Stealth” adenoviruses blunt cell-mediated and humoral immune responses against the virus and allow for significant gene expression upon readministration in the lung. J. Virol. 75, 4792–4801 (2001).
Sailaja, G., HogenEsch, H., North, A., Hays, J. & Mittal, S. K. Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector-specific immune response. Gene Ther. 9, 1722–1729 (2002).
Wakimoto, H., Fulci, G., Tyminski, E. & Chiocca, E. A. Altered expression of antiviral cytokine mRNAs associated with cyclophosphamide's enhancement of viral oncolysis. Gene Ther. 11, 214–23 (2004).
Lu, W. et al. 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. 10, 3634–3638 (2004).
Myers, R. et al. Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer. Cancer Gene Ther. 12, 593–599 (2005).
Sypula, J., Wang, F., Ma, Y., Bell, J. & McFadden, G. Myxoma virus tropism in human tumor cells. Gene Ther. Mol. Biol. 8, 103–114 (2004). First description of myxoma virus as an oncolytic agent.
Bergman, I., Whitaker-Dowling, P., Gao, Y. & Griffin, J. A. Preferential targeting of vesicular stomatitis virus to breast cancer cells. Virology 330, 24–33 (2004).
Kamizono, J. et al. Survivin-responsive conditionally replicating adenovirus exhibits cancer-specific and efficient viral replication. Cancer Res. 65, 5284–5291 (2005).
Rein, D. T. et al. A fiber-modified, secretory leukoprotease inhibitor promoter-based conditionally replicating adenovirus for treatment of ovarian cancer. Clin. Cancer Res. 11, 1327–1335 (2005).
Kanerva, A. et al. A cyclooxygenase-2 promoter-based conditionally replicating adenovirus with enhanced infectivity for treatment of ovarian adenocarcinoma. Gene Ther. 11, 552–559 (2004).
Mastrangeli, A. et al. “Sero-switch” adenovirus-mediated in vivo gene transfer: circumvention of anti-adenovirus humoral immune defenses against repeat adenovirus vector administration by changing the adenovirus serotype. Hum. Gene Ther. 7, 79–87 (1996).
Chung, R. Y., Saeki, Y. & Chiocca, E. A. B-myb promoter retargeting of herpes simplex virus γ34.5 gene-mediated virulence toward tumor and cycling cells. J. Virol. 73, 7556–7564 (1999).
Mastrangelo, M. J. et al. Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther. 6, 409–422 (1999).
J.B. and P.F. are supported by grants from CIHR, NCIC, and the Terry Fox Foundation.
The authors declare no competing financial interests.
- ENVELOPED AND NON-ENVELOPED VIRUSES
Broadly speaking, viruses can be subdivided into two groups: those that acquire a plasma membrane-derived envelope as they bud from an infected cell; or those that have only a protein coat and do not bud from the plasma membrane, but rather escape the infected cell following plasma membrane rupture.
- IMMUNOLOGICAL MEMORY
The maintenance of an expanded number of circulating antigen-specific T- and B-lymphocytes, such that subsequent encounters with the same antigen are met with a more rapid immunological response.
Any compound that, when given simultaneously with antigen, increases the immunogenicity of that antigen, increasing the immune response.
About this article
Cite this article
Parato, K., Senger, D., Forsyth, P. et al. Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer 5, 965–976 (2005). https://doi.org/10.1038/nrc1750
Advanced Healthcare Materials (2021)
Molecular Cell (2021)
Molecular Oncology (2020)
Seminars in Cancer Biology (2020)
Clinical Cancer Research (2020)