Abstract
Oncolytic virotherapy is an attractive approach that uses live viruses to selectively kill cancer cells. Oncolytic viruses can be genetically engineered to induce cell lyses through virus replication and cytotoxic protein expression. Herpes simplex virus (HSV) has become one of the most widely clinically used oncolytic agent. Various types of HSV have been studied in basic or clinical research. Combining oncolytic virotherapy with chemotherapy or radiotherapy generally produces synergic action with unclear molecular mechanisms. Arming HSV with therapeutic transgenes is a promising strategy and can be used to complement conventional therapies. As an efficient gene delivery system, HSV has been successfully used to deliver various immunomodulatory molecules. Arming HSV with therapeutic genes merits further investigation for potential clinical application.
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Parkin D M, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin, 2005, 55: 74–108
Wong H H, Lemoine N R. Biological approaches to therapy of pancreatic cancer. Pancreatology, 2008, 8: 431–461
Thorne S H. Immunotherapeutic potential of oncolytic vaccinia virus. Immunol Res, 2011, 50: 286–293
Cross D, Burmester J K. Gene therapy for cancer treatment: past, present and future. Clin Med Res, 2006, 4: 218–227
Dai M H, Zamarin D, Gao S P, et al. Synergistic action of oncolytic herpes simplex virus and radiotherapy in pancreatic cancer cell lines. Br J Surg, 2010, 97: 1385–1394
Eisenberg D P, Adusumilli P S, Hendershott K J, et al. 5-fluorouracil and gemcitabine potentiate the efficacy of oncolytic herpes viral gene therapy in the treatment of pancreatic cancer. J Gastrointest Surg, 2005, 9: 1068–1077
Hartkopf A D, Fehm T, Wallwiener D, et al. Oncolytic virotherapy of gynecologic malignancies. Gynecol Oncol, 2011, 120: 302–310
Dingwell K S, Johnson D C. The herpes simplex virus gE-gI complex facilitatescell-to-cell spread and binds to components of cell junctions. J Virol, 1998, 72: 8933–8942
De Clercq E. Antiviral drugs in current clinical use. J Clin Virol, 2004, 30: 115–133
Todo T. “Armed” oncolytic herpes simplex viruses for brain tumor therapy. Cell Adh Migr, 2008, 2: 208–213
McGeoch D J, Dalrymple M A, Davison A J, et al. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol, 1988, 69: 1531–1574
Eager R M, Nemunaitis J. Clinical development directions in oncolytic viral therapy. Cancer Gene Ther, 2011, 18: 305–317
Chou J, Kern E R, Whitley R J, et al. Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science, 1990, 250: 1262–1266
Walker J D, Sehgal I, Kousoulas K G. Oncolytic herpes simplex virus 1 encoding 15-prostaglandin dehydrogenase mitigates immune suppression and reduces ectopic primary and metastatic breast cancer in mice. J Virol, 2011, 85: 7363–7371
Haseley A, Alvarez-Breckenridge C, Chaudhury A R, et al. Advances in oncolytic virus therapy for glioma. Recent Pat CNS Drug Discov, 2009, 4: 1–13
Conrady C D, Drevets D A, Carr D J. Herpes simplex type I (HSV-1) infection of the nervous system: is an immune response a good thing? J Neuroimmunol, 2010, 220: 1–9
Kanai R, Wakimoto H, Cheema T, et al. Oncolytic herpes simplex virus vectors and chemotherapy: are combinatorial strategies more effective for cancer? Future Oncol, 2010, 6: 619–634
Fong Y, Kim T, Bhargava A, et al. A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer. Mol Ther, 2009, 17: 389–394
Martuza R L, Malick A, Markert J M, et al. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science, 1991, 252: 854–856
Markert J M, Coen D M, Malick A, et al. Expanded spectrum of viral therapy in the treatment of nervous system tumors. J Neurosurg, 1992, 77: 590–594
Markert J M, Malick A, Coen D M, et al. Reduction and elimination of encephalitis in an experimental glioma therapy model with attenuated herpes simplex mutants that retain susceptibility to acyclovir. Neurosurgery, 1993, 32: 597–603
Shirota T, Kasuya H, Kodera Y, et al. Oncolytic herpes virus induces effective anti-cancer immunity against murine colon cancer. Hepatogastroenterology, 2011, 58: 1482–1489
Watanabe I, Kasuya H, Nomura N, et al. Effects of tumor selective replication-competent herpes viruses in combination with gemcitabine on pancreatic cancer. Cancer Chemother Pharmacol, 2008, 61: 875–882
Kanzaki A, Kasuya H, Yamamura K, et al. Antitumor efficacy of oncolytic herpes simplex virus adsorbed onto antigen-specific lymphocytes. Cancer Gene Ther, 2012, 19: 292–298
Samoto K, Ehtesham M, Perng G C, et al. A herpes simplex virus type 1 mutant with gamma 34.5 and LAT deletions effectively oncolyses human U87 glioblastomas in nude mice. Neurosurgery, 2002, 50: 599–605
Samoto K, Perng G C, Ehtesham M, et al. A herpes simplex virus type 1 mutant deleted for gamma34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation. Cancer Gene Ther, 2001, 8: 269–277
Kroeger K M, Muhammad A K, Baker G J, et al. Gene therapy and virotherapy: novel therapeutic approaches for brain tumors. Discov Med, 2010, 10: 293–304
Wang J N, Hu P, Zeng M S, et al. Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma. Chin J Cancer, 2011, 30: 831–841
Passer B J, Wu C L, Wu S, et al. Analysis of genetically engineered oncolytic herpes simplex viruses in human prostate cancer organotypic cultures. Gene Ther, 2009, 16: 1477–1482
Fukuhara H, Martuza R L, Rabkin S D, et al. Oncolytic herpes simplex virus vector g47delta in combination with androgen ablation for the treatment of human prostate adenocarcinoma. Clin Cancer Res, 2005, 11: 7886–7890
Kelly K J, Wong J, Fong Y. Herpes simplex virus NV1020 as a novel and promising therapy for hepatic malignancy. Expert Opin Investig Drugs, 2008, 17: 1105–1113
McAuliffe P F, Jarnagin W R, Johnson P, et al. Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses. J Gastrointest Surg, 2000, 4: 580–588
Gutermann A, Mayer E, von Dehn-Rothfelser K, et al. Efficacy of oncolytic herpesvirus NV1020 can be enhanced by combination with chemotherapeutics in colon carcinoma cells. Hum Gene Ther, 2006, 17: 1241–1253
Cozzi P J, Malhotra S, McAuliffe P, et al. Intravesical oncolytic viral therapy using attenuated, replication-competent herpes simplex viruses G207 and Nv1020 is effective in the treatment of bladder cancer in an orthotopic syngeneic model. FASEB J, 2001, 15: 1306–1308
Ebright M I, Zager J S, Malhotra S, et al. Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model. J Thorac Cardiovasc Surg, 2002, 124: 123–129
Kemeny N, Brown K, Covey A, et al. Phase I, open-label, dose-escalating study of a genetically engineered herpes simplex virus, NV1020, in subjects with metastatic colorectal carcinoma to the liver. Hum Gene Ther, 2006, 17: 1214–1224
Geevarghese S K, Geller D A, de Haan H A, et al. Phase I/II study of oncolytic herpes simplex virus NV1020 in patients with extensively pretreated refractory colorectal cancer metastatic to the liver. Hum Gene Ther, 2010, 21: 1119–1128
Fujiwara S, Nawa A, Luo C, et al. Carrier cell-based delivery of replication-competent HSV-1 mutants enhances antitumor effect for ovarian cancer. Cancer Gene Ther, 2011, 18: 77–86
Watanabe D, Goshima F, Mori I, et al. Oncolytic virotherapy for malignant melanoma with herpes simplex virus type 1 mutant HF10. J Dermatol Sci, 2008, 50: 185–196
Kimata H, Imai T, Kikumori T, et al. Pilot study of oncolytic viral therapy using mutant herpes simplex virus (HF10) against recurrent metastatic breast cancer. Ann Surg Oncol, 2006, 13: 1078–1084
Nakao A, Kasuya H, Sahin T T, et al. 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 Ther, 2011, 18: 167–175
Sahin T T, Kasuya H, Nomura N, et al. Impact of novel oncolytic virus HF10 on cellular components of the tumor microenvironment in patients with recurrent breast cancer. Cancer Gene Ther, 2012, 19: 229–237
Rampling R, Cruickshank G, Papanastassiou V, et al. Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther, 2000, 7: 859–866
Mace A T, Ganly I, Soutar D S, et al. Potential for efficacy of the oncolytic herpes simplex virus 1716 in patients with oral squamous cell carcinoma. Head & Neck, 2008, 30: 1045–1051
Papanastassiou V, Rampling R, Fraser M, et al. The potential for efficacy of the modified (ICP 34.5(−)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study. Gene Ther, 2002, 9: 398–406
Harrow S, Papanastassiou V, Harland J, 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, 2004, 11: 1648–1658
Hu J C, Coffin R S, Davis C J, et al. A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res, 2006, 12: 6737–6747
Kaufman H L, Kim D W, DeRaffele G, et al. Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma. Ann Surg Oncol, 2010, 17: 718–730
Kaufman H L, Bines S D. OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol, 2010, 6: 941–949
OPTiM OncoVEXGM-CSF Phase III Trial in Melanoma. www.oncovexgmcsf.com
Fu X, Tao L, Cai R, et al. A mutant type 2 herpes simplex virus deleted for the protein kinase domain of the ICP10 gene is a potent oncolytic virus. Mol Ther, 2006, 13: 882–890
Fu X, Nakamori M, Tao L, et al. Antitumor effects of two newly constructed oncolytic herpes simplex viruses against renal cell carcinoma. Int J Oncol, 2007, 30: 1561–1567
Fu X, Tao L, Zhang X. An oncolytic virus derived from type 2 herpes simplex virus has potent therapeutic effect against metastatic ovarian cancer. Cancer Gene Ther, 2007, 14: 480–487
Fu X, Tao L, Li M, et al. Effective treatment of pancreatic cancer xenografts with a conditionally replicating virus derived from type 2 herpes simplex virus. Clin Cancer Res, 2006, 12: 3152–3157
Li H, Dutuor A, Fu X, et al. Induction of strong antitumor immunity by an HSV-2-based oncolytic virus in a murine mammary tumor model. J Gene Med, 2007, 9: 161–169
Li H, Zeng Z, Fu X, et al. Coadministration of a herpes simplex virus-2 based oncolytic virus and cyclophosphamide produces a synergistic antitumor effect and enhances tumor-specific immune responses. Cancer Res, 2007, 67: 7850–7855
Post D E, Fulci G, Chiocca E A, et al. Replicative oncolytic herpes simplex viruses in combination cancer therapies. Curr Gene Ther, 2004, 4: 41–51
Blank S V, Rubin S C, Coukos G, et al. Replication-selective herpes simplex virus type 1 mutant therapy of cervical cancer is enhanced by low-dose radiation. Hum Gene Ther, 2002, 13: 627–639
Passer B J, Castelo-Branco P, Buhrman J S, et al. Oncolytic herpes simplex virus vectors and taxanes synergize to promote killing of prostate cancer cells. Cancer Gene Ther, 2009, 16: 551–560
Advani S J, Mezhir J J, Roizman B, et al. ReVOLT: radiation-enhanced viral oncolytic therapy. Int J Radiat Oncol Biol Phys, 2006, 66: 637–646
Ottolino-Perry K, Diallo J S, Lichty B D, et al. Intelligent design: combination therapy with oncolytic viruses. Mol Ther, 2010, 18: 251–263
Kim S H, Wong R J, Kooby D A, et al. Combination of mutated herpes simplex virus type 1 (G207 virus) with radiation for the treatment of squamous cell carcinoma of the head and neck. Eur J Cancer, 2005, 41: 313–322
Jarnagin W R, Zager J S, Hezel M, et al. Treatment of cholangio-carcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy. Cancer Gene Ther, 2006, 13: 326–334
Adusumilli P S, Stiles B M, Chan M K, et al. Radiation therapy potentiates effective oncolytic viral therapy in the treatment of lung cancer. Ann Thorac Surg, 2005, 80: 409–417
Stanziale S F, Petrowsky H, Joe J K, et al. Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex virus G207 by upregulating ribonucleotide reductase. Surgery, 2002, 132: 353–359
Petrowsky H, Roberts G, Kooby D A, et al. Functional interaction between fluorodeoxyuridine-induced cellular alterations and replication of a ribonucleotide reductase-negative herpes simplex virus. J Virol, 2001, 75: 7050–7108
Hu J C, Hallden G, Shorrock C, et al. Combination of a second generation genetically modified herpes simplex virus 1 (HSV1) with paclitaxel in the treatment of breast cancer in vitro. In: ASCO Annual Meeting Proceedings, 2004. 22: 723
Ottolino-Perry K, Diallo J S, Lichty B D, et al. Intelligent design: combination therapy with oncolytic viruses. Mol Ther, 2010, 18: 251–263
Wong H H, Lemoine N R, Wang Y. Oncolytic viruses for cancer therapy: overcoming the obstacles. Viruses, 2010, 2: 78–106
Shah A C, Benos D, Gillespie G Y, et al. Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas. J Neurooncol, 2003, 65: 203–226
Wong R J, Chan M K, Yu Z, et al. Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12. Clin Cancer Res, 2004, 10: 4509–4516
Derubertis B G, Stiles B M, Bhargava A, et al. Cytokine-secreting herpes viral mutants effectively treat tumor in a murine metastatic colorectal liver model by oncolytic and T-cell-dependent mechanisms. Cancer Gene Ther, 2007, 14: 590–597
Wong R J, Chan M K, Yu Z, et al. Effective intravenous therapy of murine pulmonary metastases with an oncolytic herpes virus expressing interleukin 12. Clin Cancer Res, 2004, 10: 251–259
Wong R J, Patel S G, Kim S, et al. Cytokine gene transfer enhances herpes oncolytic therapy in murine squamous cell carcinoma. Hum Gene Ther, 2001, 12: 253–265
Campadelli-Fiume G, De Giovanni C, Gatta V, et al. Rethinking herpes simplex virus: the way to oncolytic agents. Rev Med Virol, 2011, 21: 213–226
Serafini P, Carbley R, Noonan K A, et al. High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res, 2004, 64: 6337–6343
Kaur B, Cripe T P, Chiocca E A. “Buy one get one free”: armed viruses for the treatment of cancer cells and their microenvironment. Curr Gene Ther, 2009, 9: 341–355
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Liu, S., Dai, M., You, L. et al. Advance in herpes simplex viruses for cancer therapy. Sci. China Life Sci. 56, 298–305 (2013). https://doi.org/10.1007/s11427-013-4466-4
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DOI: https://doi.org/10.1007/s11427-013-4466-4