Hostname: page-component-76fb5796d-skm99 Total loading time: 0 Render date: 2024-04-25T16:42:55.767Z Has data issue: false hasContentIssue false

Oncolytic virotherapy for pancreatic cancer

Published online by Cambridge University Press:  18 May 2011

Sonia Wennier
Affiliation:
Molecular Genetics and Microbiology Department, University of Florida, Gainesville, USA
Shoudong Li
Affiliation:
Molecular Genetics and Microbiology Department, University of Florida, Gainesville, USA
Grant McFadden*
Affiliation:
Molecular Genetics and Microbiology Department, University of Florida, Gainesville, USA
*
*Corresponding author: Grant McFadden, University of Florida, 1600 SW Archer Road, PO Box 100266, Gainesville, FL 32610, USA. E-mail: grantmcf@ufl.edu

Abstract

Within the past decade, many oncolytic viruses (OVs) have been studied as potential treatments for pancreatic cancer and some of these are currently under clinical trials. The applicability of certain OVs, such as adenoviruses, herpesviruses and reoviruses, for the treatment of pancreatic cancer has been intensively studied for several years, whereas the applicability of other more recently investigated OVs, such as poxviruses and parvoviruses, is only starting to be determined. At the same time, studies have identified key characteristics of pancreatic cancer biology that provide a better understanding of the important factors or pathways involved in this disease. This review aims to summarise the different replication-competent OVs proposed as therapeutics for pancreatic cancer. It also focuses on the unique biology of these viruses that makes them exciting candidate virotherapies for pancreatic cancer and discusses how they could be genetically manipulated or combined with other drugs to improve their efficacy based on what is currently known about the molecular biology of pancreatic cancer.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Jemal, A. et al. (2010) Cancer statistics, 2010. CA: A Cancer Journal for Clinicians 60, 277-300Google ScholarPubMed
2Basturk, O., Coban, I. and Adsay, N.V. (2010) Biological classification and biological behavior of pancreatic neoplasia. In Pancreatic Cancer (Neoptolemos, J.P., Urrutia, R., Abbruzzese, J. and Buchler, M., eds), pp. 40-70. Springer Science and Business Media, New YorkGoogle Scholar
3Rozenblum, E. et al. (1997) Tumor-suppressive pathways in pancreatic carcinoma. Cancer Research 57, 1731-1734Google ScholarPubMed
4Almoguera, C. et al. (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53, 549-554CrossRefGoogle ScholarPubMed
5Adjei, A.A. (2001) Blocking oncogenic Ras signaling for cancer therapy. Journal of the National Cancer Institute 93, 1062-1074CrossRefGoogle ScholarPubMed
6Grippo, P.J. et al. (2003) Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice. Cancer Research 63, 2016-2019Google ScholarPubMed
7Aguirre, A.J. et al. (2003) Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes and Development 17, 3112-3126CrossRefGoogle ScholarPubMed
8Bardeesy, N. et al. (2006) Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proceedings of the National Academy of Sciences of the United States of America 103, 5947-5952CrossRefGoogle ScholarPubMed
9Jones, S. et al. (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801-1806CrossRefGoogle ScholarPubMed
10Chu, G.C. et al. (2007) Stromal biology of pancreatic cancer. Journal of Cellular Biochemistry 101, 887-907CrossRefGoogle ScholarPubMed
11Olive, K.P. et al. (2009) Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324, 1457-1461CrossRefGoogle Scholar
12Shah, A.N. et al. (2007) Development and characterization of gemcitabine-resistant pancreatic tumor cells. Annals of the Surgical Oncology 14, 3629-3637CrossRefGoogle ScholarPubMed
13Wang, Z. et al. (2009) Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Research 69, 2400-2407CrossRefGoogle ScholarPubMed
14Thiery, J.P. et al. (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-890CrossRefGoogle ScholarPubMed
15Joo, Y.E. et al. (2002) Expression of E-cadherin, alpha- and beta-catenins in patients with pancreatic adenocarcinoma. Pancreatology 2, 129-137CrossRefGoogle ScholarPubMed
16Nakajima, S. et al. (2004) N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma. Clinical Cancer Research 10(12 Pt 1), 4125-4133CrossRefGoogle ScholarPubMed
17Arumugam, T. et al. (2009) Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Research 69, 5820-5828CrossRefGoogle ScholarPubMed
18Burris, H.A. III, et al. (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. Journal of Clinical Oncology 15, 2403-2413CrossRefGoogle ScholarPubMed
19Hertel, L.W. et al. (1990) Evaluation of the antitumor activity of gemcitabine (2′,2′-difluoro-2′-deoxycytidine). Cancer Research 50, 4417-4422Google Scholar
20Huang, P. et al. (1991) Action of 2′,2′-difluorodeoxycytidine on DNA synthesis. Cancer Research 51, 6110-6117Google ScholarPubMed
21Colucci, G. et al. (2002) Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale. Cancer 94, 902-910CrossRefGoogle ScholarPubMed
22Louvet, C. et al. (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. Journal of Clinical Oncology 23, 3509-3516CrossRefGoogle ScholarPubMed
23Rocha Lima, C.M. et al. (2004) Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. Journal of Clinical Oncology 22, 3776-3783CrossRefGoogle ScholarPubMed
24Kulke, M.H. et al. (2009) Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904. Journal of Clinical Oncology 27, 5506-5512CrossRefGoogle ScholarPubMed
25Rocha-Lima, C.M. and Raez, L.E. (2009) Erlotinib (tarceva) for the treatment of non-small-cell lung cancer and pancreatic cancer. Pharmacy and Therapeutics 34, 554-564Google ScholarPubMed
26Moore, M.J. et al. (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. Journal of Clinical Oncology 25, 1960-1966CrossRefGoogle ScholarPubMed
27Conroy, T. et al. (2005) Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer – a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. Journal of Clinical Oncology 23, 1228-1236CrossRefGoogle ScholarPubMed
28Kim, R. (2010) FOLFIRINOX: a new standard treatment for advanced pancreatic cancer? Lancet Oncology 12, 8-9CrossRefGoogle ScholarPubMed
29Plentz, R.R., Manns, M.P. and Greten, T.F. (2010) Molecular therapy of pancreatic cancer. Minerva Endocrinologica 35, 27-33Google ScholarPubMed
30Mackenzie, R.P. and McCollum, A.D. (2009) Novel agents for the treatment of adenocarcinoma of the pancreas. Expert Review of Anticancer Therapy 9, 1473-1485CrossRefGoogle ScholarPubMed
31Davis, J.J. and Fang, B. (2005) Oncolytic virotherapy for cancer treatment: challenges and solutions. Journal of Gene Medicine 7, 1380-1389CrossRefGoogle ScholarPubMed
32Vaha-Koskela, M.J., Heikkila, J.E. and Hinkkanen, A.E. (2007) Oncolytic viruses in cancer therapy. Cancer Letters 254, 178-216CrossRefGoogle ScholarPubMed
33Bischoff, J.R. et al. (1996) An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274, 373-376CrossRefGoogle ScholarPubMed
34O'Shea, C.C. et al. (2004) Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity. Cancer Cell 6, 611-623CrossRefGoogle ScholarPubMed
35Heise, C. et al. (2000) An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nature Medicine 6, 1134-1139CrossRefGoogle ScholarPubMed
36Fueyo, J. et al. (2000) A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 19, 2-12CrossRefGoogle ScholarPubMed
37Leitner, S. et al. (2009) Oncolytic adenoviral mutants with E1B19K gene deletions enhance gemcitabine-induced apoptosis in pancreatic carcinoma cells and anti-tumor efficacy in vivo. Clinical Cancer Research 15, 1730-1740CrossRefGoogle ScholarPubMed
38Yoon, S.S. et al. (1998) Cancer gene therapy using a replication-competent herpes simplex virus type 1 vector. Annals of Surgery 228, 366-374CrossRefGoogle ScholarPubMed
39Smith, K.D. et al. (2006) Activated MEK suppresses activation of PKR and enables efficient replication and in vivo oncolysis by Deltagamma(1)34.5 mutants of herpes simplex virus 1. Journal of Virology 80, 1110-1120CrossRefGoogle Scholar
40Sarinella, F. et al. (2006) Oncolysis of pancreatic tumour cells by a gamma34.5-deleted HSV-1 does not rely upon Ras-activation, but on the PI 3-kinase pathway. Gene Therapy 13, 1080-1087CrossRefGoogle Scholar
41Smith, C.C. et al. (2000) Ras-GAP binding and phosphorylation by herpes simplex virus type 2 RR1 PK (ICP10) and activation of the Ras/MEK/MAPK mitogenic pathway are required for timely onset of virus growth. Journal of Virology 74, 10417-10429CrossRefGoogle ScholarPubMed
42Rommelaere, J. et al. (2010) Oncolytic parvoviruses as cancer therapeutics. Cytokine and Growth Factor Reviews 21, 185-195CrossRefGoogle ScholarPubMed
43Dempe, S. et al. (2010) SMAD4: a predictive marker of PDAC cell permissiveness for oncolytic infection with parvovirus H-1PV. International Journal of Cancer 126, 2914-2927CrossRefGoogle ScholarPubMed
44Riolobos, L. et al. (2010) Viral oncolysis that targets Raf-1 signaling control of nuclear transport. Journal of Virology 84, 2090-2099CrossRefGoogle ScholarPubMed
45Strong, J.E. et al. (1998) The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO Journal 17, 3351-3362CrossRefGoogle ScholarPubMed
46Thorne, S.H., Hwang, T.H. and Kirn, D.H. (2005) Vaccinia virus and oncolytic virotherapy of cancer. Current Opinion in Molecular Therapeutics 7, 359-365Google ScholarPubMed
47Kirn, D.H. and Thorne, S.H. (2009) Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer. Nature Reviews. Cancer 9, 64-71CrossRefGoogle ScholarPubMed
48Wang, G. et al. (2006) Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor. Proceedings of the National Academy of Sciences of the United States of America 103, 4640-4645CrossRefGoogle ScholarPubMed
49Kim, M. et al. (2010) The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status. Oncogene 29, 3990-3996CrossRefGoogle ScholarPubMed
50Galanis, E. (2010) Therapeutic potential of oncolytic measles virus: promises and challenges. Clinical Pharmacology and Therapeutics 88, 620-625CrossRefGoogle Scholar
51Paraskevakou, G. et al. (2007) Epidermal growth factor receptor (EGFR)-retargeted measles virus strains effectively target EGFR- or EGFRvIII expressing gliomas. Molecular Therapy 15, 677-686CrossRefGoogle ScholarPubMed
52Kinoh, H. et al. (2009) Generation of optimized and urokinase-targeted oncolytic Sendai virus vectors applicable for various human malignancies. Gene Therapy 16, 392-403CrossRefGoogle ScholarPubMed
53Spencer, J.F. et al. (2009) New pancreatic carcinoma model for studying oncolytic adenoviruses in the permissive Syrian hamster. Cancer Gene Therapy 16, 912-922CrossRefGoogle ScholarPubMed
54O'Shea, C.C. et al. (2005) Heat shock phenocopies E1B-55K late functions and selectively sensitizes refractory tumor cells to ONYX-015 oncolytic viral therapy. Cancer Cell 8, 61-74CrossRefGoogle ScholarPubMed
55Heise, C. et al. (1997) ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nature Medicine 3, 639-645CrossRefGoogle ScholarPubMed
56Mymryk, J.S. (1996) Tumour suppressive properties of the adenovirus 5 E1A oncogene. Oncogene 13, 1581-1589Google ScholarPubMed
57Oberg, D. et al. (2010) Improved potency and selectivity of an oncolytic E1ACR2 and E1B19K deleted adenoviral mutant in prostate and pancreatic cancers. Clinical Cancer Research 16, 541-553CrossRefGoogle ScholarPubMed
58Kamphaus, G.D. et al. (2000) Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. Journal of Biological Chemistry 275, 1209-1215CrossRefGoogle ScholarPubMed
59Delesque, N. et al. (1997) sst2 somatostatin receptor expression reverses tumorigenicity of human pancreatic cancer cells. Cancer Research 57, 956-962Google ScholarPubMed
60Zhang, Z. et al. (2009) Reexpression of human somatostatin receptor gene 2 gene mediated by oncolytic adenovirus increases antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand against pancreatic cancer. Clinical Cancer Research 15, 5154-5160CrossRefGoogle ScholarPubMed
61Freytag, S.O. et al. (2007) Replication-competent adenovirus-mediated suicide gene therapy with radiation in a preclinical model of pancreatic cancer. Molecular Therapy 15, 1600-1606CrossRefGoogle Scholar
62Ramirez, P.J. et al. (2008) Optimization of conditionally replicative adenovirus for pancreatic cancer and its evaluation in an orthotopic murine xenograft model. American Journal of Surgery 195, 481-490CrossRefGoogle Scholar
63Wang, H. et al. (2011) Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nature Medicine 17, 96-104CrossRefGoogle Scholar
64Nishimoto, T. et al. (2009) Oncolytic virus therapy for pancreatic cancer using the adenovirus library displaying random peptides on the fiber knob. Gene Therapy 16, 669-680CrossRefGoogle ScholarPubMed
65Nelson, A.R. et al. (2009) Combination of conditionally replicative adenovirus and standard chemotherapies shows synergistic antitumor effect in pancreatic cancer. Cancer Science 100, 2181-2187CrossRefGoogle ScholarPubMed
66Huch, M. et al. (2009) Urokinase-type plasminogen activator receptor transcriptionally controlled adenoviruses eradicate pancreatic tumors and liver metastasis in mouse models. Neoplasia 11, 518-528, 4 p following 28CrossRefGoogle ScholarPubMed
67Onimaru, M. et al. (2010) hTERT-promoter-dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication-defective adenovirus vectors in pancreatic cancer cells. Cancer Science 101, 735-742CrossRefGoogle ScholarPubMed
68Bortolanza, S. et al. (2009) Treatment of pancreatic cancer with an oncolytic adenovirus expressing interleukin-12 in Syrian hamsters. Molecular Therapy 17, 614-622CrossRefGoogle ScholarPubMed
69Molina, M.A. et al. (1999) Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Research 59, 4356-4362Google ScholarPubMed
70Mihaljevic, A.L. et al. (2010) Molecular mechanism of pancreatic cancer – -understanding proliferation, invasion, and metastasis. Langenbecks Arch Surg 395, 295-308CrossRefGoogle ScholarPubMed
71Onimaru, M. et al. (2010) Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer. Cancer Letters 294, 178-186CrossRefGoogle ScholarPubMed
72He, B., Gross, M. and Roizman, B. (1997) 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. Proceedings of the National Academy of Sciences of the United States of America 94, 843-848CrossRefGoogle ScholarPubMed
73Mundschau, L.J. and Faller, D.V. (1994) Endogenous inhibitors of the dsRNA-dependent eIF-2 alpha protein kinase PKR in normal and ras-transformed cells. Biochimie 76, 792-800CrossRefGoogle ScholarPubMed
74Mineta, T. et al. (1995) Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nature Medicine 1, 938-943CrossRefGoogle ScholarPubMed
75Meignier, B., Longnecker, R. and Roizman, B. (1988) In vivo behavior of genetically engineered herpes simplex viruses R7017 and R7020: construction and evaluation in rodents. Journal of Infectious Diseases 158, 602-614CrossRefGoogle ScholarPubMed
76Varghese, S. and Rabkin, S.D. (2002) Oncolytic herpes simplex virus vectors for cancer virotherapy. Cancer Gene Therapy 9, 967-978CrossRefGoogle ScholarPubMed
77Liu, B.L. et al. (2003) ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Therapy 10, 292-303CrossRefGoogle ScholarPubMed
78Kimata, H. et al. (2003) Effective treatment of disseminated peritoneal colon cancer with new replication-competent herpes simplex viruses. Hepatogastroenterology 50, 961-966Google ScholarPubMed
79Kasuya, H. et al. (2007) Suitability of a US3-inactivated HSV mutant (L1BR1) as an oncolytic virus for pancreatic cancer therapy. Cancer Gene Therapy 14, 533-542CrossRefGoogle ScholarPubMed
80Fu, X. et al. (2006) Effective treatment of pancreatic cancer xenografts with a conditionally replicating virus derived from type 2 herpes simplex virus. Clinical Cancer Research 12, 3152-3157CrossRefGoogle ScholarPubMed
81Kasuya, H. et al. (1999) Intraperitoneal delivery of hrR3 and ganciclovir prolongs survival in mice with disseminated pancreatic cancer. Journal of Surgical Oncology 72, 136-1413.0.CO;2-3>CrossRefGoogle ScholarPubMed
82Watanabe, I. et al. (2008) Effects of tumor selective replication-competent herpes viruses in combination with gemcitabine on pancreatic cancer. Cancer Chemotherapy and Pharmacology 61, 875-882CrossRefGoogle ScholarPubMed
83McAuliffe, P.F. et al. (2000) Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses. Journal of Gastrointestinal Surgery 4, 580-588CrossRefGoogle ScholarPubMed
84Gil, Z. et al. (2007) Nerve-sparing therapy with oncolytic herpes virus for cancers with neural invasion. Clinical Cancer Research 13, 6479-6485CrossRefGoogle ScholarPubMed
85Simpson, G.R. et al. (2006) Combination of a fusogenic glycoprotein, prodrug activation, and oncolytic herpes simplex virus for enhanced local tumor control. Cancer Research 66, 4835-4842CrossRefGoogle ScholarPubMed
86Shaughnessy, E. et al. (1996) Parvoviral vectors for the gene therapy of cancer. Seminars in Oncology 23, 159-171Google ScholarPubMed
87Angelova, A.L. et al. (2009) Improvement of gemcitabine-based therapy of pancreatic carcinoma by means of oncolytic parvovirus H-1PV. Clinical Cancer Research 15, 511-519CrossRefGoogle ScholarPubMed
88Bhat, R. et al. (2011) Enhancement of NK cell anti-tumour responses using an oncolytic parvovirus. International Journal of Cancer 128, 908-919CrossRefGoogle Scholar
89Grekova, S. et al. (2010) Immune cells participate in the oncosuppressive activity of parvovirus H-1PV and are activated as a result of their abortive infection with this agent. Cancer Biology and Therapy 10, 52-61CrossRefGoogle ScholarPubMed
90Etoh, T. et al. (2003) Oncolytic viral therapy for human pancreatic cancer cells by reovirus. Clinical Cancer Research 9, 1218-1223Google ScholarPubMed
91Himeno, Y. et al. (2005) Efficacy of oncolytic reovirus against liver metastasis from pancreatic cancer in immunocompetent models. International Journal of Oncology 27, 901-906Google ScholarPubMed
92Hirano, S. et al. (2009) Reovirus inhibits the peritoneal dissemination of pancreatic cancer cells in an immunocompetent animal model. Oncology Reports 21, 1381-1384CrossRefGoogle Scholar
93Evgin, L. et al. (2010) Potent oncolytic activity of raccoonpox virus in the absence of natural pathogenicity. Molecular Therapy 18, 896-902CrossRefGoogle ScholarPubMed
94Kaufman, H.L. et al. (2007) Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer. Journal of Translational Medicine 5, 60CrossRefGoogle ScholarPubMed
95Petrulio, C.A. and Kaufman, H.L. (2006) Development of the PANVAC-VF vaccine for pancreatic cancer. Expert Reviews of Vaccines 5, 9-19CrossRefGoogle ScholarPubMed
96Kantor, J. et al. (1992) Antitumor activity and immune responses induced by a recombinant carcinoembryonic antigen-vaccinia virus vaccine. Journal of the National Cancer Institute 84, 1084-1091CrossRefGoogle ScholarPubMed
97Yu, Y.A. et al. (2009) Regression of human pancreatic tumor xenografts in mice after a single systemic injection of recombinant vaccinia virus GLV-1h68. Molecular Cancer Therapeutics 8, 141-151CrossRefGoogle ScholarPubMed
98Hiley, C.T. et al. (2010) Lister strain vaccinia virus, a potential therapeutic vector targeting hypoxic tumours. Gene Therapy 17, 281-287CrossRefGoogle ScholarPubMed
99Tysome, J.R. et al. (2009) Lister strain of vaccinia virus armed with endostatin-angiostatin fusion gene as a novel therapeutic agent for human pancreatic cancer. Gene Therapy 16, 1223-1233CrossRefGoogle ScholarPubMed
100Sypula, J. et al. (2004) Myxoma virus tropism in human tumor cells. Gene Therapy and Molecular Biology 8, 103-114Google Scholar
101Lun, X.Q. et al. (2007) Targeting human medulloblastoma: oncolytic virotherapy with myxoma virus is enhanced by rapamycin. Cancer Research 67, 8818-8827CrossRefGoogle ScholarPubMed
102Stanford, M.M. et al. (2008) Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo. Molecular Therapy 16, 52-59CrossRefGoogle ScholarPubMed
103Wu, Y. et al. (2008) Oncolytic efficacy of recombinant vesicular stomatitis virus and myxoma virus in experimental models of rhabdoid tumors. Clinical Cancer Research 14, 1218-1227CrossRefGoogle ScholarPubMed
104Lun, X. et al. (2005) Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. Cancer Research 65, 9982-9990CrossRefGoogle ScholarPubMed
105Woo, Y. et al. (2008) Myxoma virus is oncolytic for human pancreatic adenocarcinoma cells. Annals of the Surgical Oncology 15, 2329-2335CrossRefGoogle ScholarPubMed
106Radecke, F. et al. (1995) Rescue of measles viruses from cloned DNA. EMBO Journal 14, 5773-5784CrossRefGoogle ScholarPubMed
107Carlson, S.K. et al. (2009) Quantitative molecular imaging of viral therapy for pancreatic cancer using an engineered measles virus expressing the sodium-iodide symporter reporter gene. AJR. American Journal of Roentgenology 192, 279-287CrossRefGoogle ScholarPubMed
108Yu, W. and Fang, H. (2007) Clinical trials with oncolytic adenovirus in China. Current Cancer Drug Targets 7, 141-148CrossRefGoogle ScholarPubMed
109Mulvihill, S. et al. (2001) Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial. Gene Therapy 8, 308-315CrossRefGoogle ScholarPubMed
110Hecht, J.R. et al. (2003) A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. Clinical Cancer Research 9, 555-561Google ScholarPubMed
111Nakao, A. et al. (2011) A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer. Cancer Gene Therapy 18, 167-175CrossRefGoogle ScholarPubMed
112Forsyth, P. et al. (2008) A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas. Molecular Therapy 16, 627-632CrossRefGoogle ScholarPubMed
113Vidal, L. et al. (2008) A phase I study of intravenous oncolytic reovirus type 3 Dearing in patients with advanced cancer. Clinical Cancer Research 14, 7127-7137CrossRefGoogle ScholarPubMed
114White, C.L. et al. (2008) Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial. Gene Therapy 15, 911-920CrossRefGoogle ScholarPubMed
115Harrington, K.J. et al. (2010) Clinical trials with oncolytic reovirus: moving beyond phase I into combinations with standard therapeutics. Cytokine and Growth Factor Reviews 21, 91-98CrossRefGoogle ScholarPubMed
116Worschech, A. et al. (2009) The immunologic aspects of poxvirus oncolytic therapy. Cancer Immunology and Immunotherapy 58, 1355-1362CrossRefGoogle ScholarPubMed
117Boisgerault, N., Tangy, F. and Gregoire, M. (2010) New perspectives in cancer virotherapy: bringing the immune system into play. Immunotherapy 2, 185-199CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

Ottolino-Perry, K. et al. (2009). Intelligent design: combination therapy with oncolytic viruses. Molecular Therapy 18, 251-263CrossRefGoogle ScholarPubMed
Power, A.T. and Bell, J.C. (2008) Taming the Trojan horse: optimizing dynamic carrier cell/oncolytic virus systems for cancer biotherapy. Gene Therapy 15, 772-779CrossRefGoogle ScholarPubMed
Cattaneo, R. et al. (2008) Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nature Reviews. Microbiology 6, 529-540CrossRefGoogle ScholarPubMed
Liu, T.C., Galanis, E. and Kirn, D. (2007) Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress. Nature Clinical Practice. Oncology 4, 101-117CrossRefGoogle ScholarPubMed