Current standard treatments of cancer can prolong survival of many cancer patients but usually do not effectively cure the disease. Oncolytic virotherapy is an emerging therapeutic for the treatment of cancer that exploits replication-competent viruses to selectively infect and destroy cancerous cells while sparing normal cells and tissues. Clinical and/or preclinical studies on oncolytic viruses have revealed that the candidate viruses being tested in trials are remarkably safe and offer potential for treating many classes of currently incurable cancers. Among these candidates are vaccinia and myxoma viruses, which belong to the family Poxviridae and possess promising oncolytic features. This article describes poxviruses that are being developed for oncolytic virotherapy and summarizes the outcomes of both clinical and preclinical studies. Additionally, studies demonstrating superior efficacy when poxvirus oncolytic virotherapy is combined with conventional therapies are described.

Associated Article

There are media items related to this article:
Oncolytic Poxviruses

Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Breitbach CJ, Reid T, Burke J, Bell JC, Kirn DH. 1.  2010. Navigating the clinical development landscape for oncolytic viruses and other cancer therapeutics: no shortcuts on the road to approval. Cytokine Growth Factor Rev. 21:85–89 [Google Scholar]
  2. Donnelly O, Harrington K, Melcher A, Pandha H. 2.  2013. Live viruses to treat cancer. J. R. Soc. Med. 106:310–14 [Google Scholar]
  3. Donnelly OG, Errington-Mais F, Prestwich R, Harrington K, Pandha H. 3.  et al. 2012. Recent clinical experience with oncolytic viruses. Curr. Pharm. Biotechnol. 13:1834–41 [Google Scholar]
  4. Eager RM, Nemunaitis J. 4.  2011. Clinical development directions in oncolytic viral therapy. Cancer Gene Ther. 18:305–17 [Google Scholar]
  5. Miest TS, Cattaneo R. 5.  2014. New viruses for cancer therapy: meeting clinical needs. Nat. Rev. Microbiol. 12:23–34 [Google Scholar]
  6. Patel MR, Kratzke RA. 6.  2013. Oncolytic virus therapy for cancer: the first wave of translational clinical trials. Transl. Res. 161:355–64 [Google Scholar]
  7. Sze DY, Reid TR, Rose SC. 7.  2013. Oncolytic virotherapy. J. Vasc. Interv. Radiol. 24:1115–22 [Google Scholar]
  8. Vacchelli E, Eggermont A, Sautes-Fridman C, Galon J, Zitvogel L. 8.  et al. 2013. Trial watch: oncolytic viruses for cancer therapy. Oncoimmunology 2:e24612 [Google Scholar]
  9. Russell SJ, Peng KW, Bell JC. 9.  2012. Oncolytic virotherapy. Nat. Biotechnol. 30:658–70 [Google Scholar]
  10. Bell J, McFadden G. 10.  2014. Viruses for tumor therapy. Cell Host Microbe 15:260–65 [Google Scholar]
  11. Moss B. 11.  2013. Poxviridae. Fields Virology BN Fields, DM Knipe, PM Howley 2129–59 Philadelphia: Lippincott Williams & Wilkins [Google Scholar]
  12. Appleyard G, Hapel AJ, Boulter EA. 12.  1971. An antigenic difference between intracellular and extracellular rabbitpox virus. J. Gen. Virol. 13:9–17 [Google Scholar]
  13. Boulter EA, Appleyard G. 13.  1973. Differences between extracellular and intracellular forms of poxvirus and their implications. Prog. Med. Virol. 16:86–108 [Google Scholar]
  14. McFadden G. 14.  2005. Poxvirus tropism. Nat. Rev. Microbiol. 3:201–13 [Google Scholar]
  15. Bengali Z, Townsley AC, Moss B. 15.  2009. Vaccinia virus strain differences in cell attachment and entry. Virology 389:132–40 [Google Scholar]
  16. Chan WM, Bartee EC, Moreb JS, Dower K, Connor JH, McFadden G. 16.  2013. Myxoma and vaccinia viruses bind differentially to human leukocytes. J. Virol. 87:4445–60 [Google Scholar]
  17. Chiu WL, Lin CL, Yang MH, Tzou DL, Chang W. 17.  2007. Vaccinia virus 4c (A26L) protein on intracellular mature virus binds to the extracellular cellular matrix laminin. J. Virol. 81:2149–57 [Google Scholar]
  18. Chung CS, Hsiao JC, Chang YS, Chang W. 18.  1998. A27L protein mediates vaccinia virus interaction with cell surface heparan sulfate. J. Virol. 72:1577–85 [Google Scholar]
  19. Moss B. 19.  2012. Poxvirus cell entry: How many proteins does it take?. Viruses 4:688–707 [Google Scholar]
  20. Mercer J, Helenius A. 20.  2008. Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells. Science 320:531–35 [Google Scholar]
  21. Mercer J, Helenius A. 21.  2010. Apoptotic mimicry: phosphatidylserine-mediated macropinocytosis of vaccinia virus. Ann. N.Y. Acad. Sci.120949–55 [Google Scholar]
  22. Mercer J, Knebel S, Schmidt FI, Crouse J, Burkard C, Helenius A. 22.  2010. Vaccinia virus strains use distinct forms of macropinocytosis for host-cell entry. Proc. Natl. Acad. Sci. USA 107:9346–51 [Google Scholar]
  23. Hiller G, Weber K. 23.  1985. Golgi-derived membranes that contain an acylated viral polypeptide are used for vaccinia virus envelopment. J. Virol. 55:651–59 [Google Scholar]
  24. Schmelz M, Sodeik B, Ericsson M, Wolffe EJ, Shida H. 24.  et al. 1994. Assembly of vaccinia virus: The second wrapping cisterna is derived from the trans Golgi network. J. Virol. 68:130–47 [Google Scholar]
  25. Tooze J, Hollinshead M, Reis B, Radsak K, Kern H. 25.  1993. Progeny vaccinia and human cytomegalovirus particles utilize early endosomal cisternae for their envelopes. Eur. J. Cell Biol. 60:163–78 [Google Scholar]
  26. Hollinshead M, Rodger G, Van Eijl H, Law M, Hollinshead R. 26.  et al. 2001. Vaccinia virus utilizes microtubules for movement to the cell surface. J. Cell Biol. 154:389–402 [Google Scholar]
  27. Ward BM. 27.  2011. The taking of the cytoskeleton one two three: how viruses utilize the cytoskeleton during egress. Virology 411:244–50 [Google Scholar]
  28. Payne LG. 28.  1980. Significance of extracellular enveloped virus in the in vitro and in vivo dissemination of vaccinia. J. Gen. Virol. 50:89–100 [Google Scholar]
  29. Smith GL, Vanderplasschen A, Law M. 29.  2002. The formation and function of extracellular enveloped vaccinia virus. J. Gen. Virol. 83:2915–31 [Google Scholar]
  30. Ichihashi Y. 30.  1996. Extracellular enveloped vaccinia virus escapes neutralization. Virology 217:478–85 [Google Scholar]
  31. Vanderplasschen A, Mathew E, Hollinshead M, Sim RB, Smith GL. 31.  1998. Extracellular enveloped vaccinia virus is resistant to complement because of incorporation of host complement control proteins into its envelope. Proc. Natl. Acad. Sci. USA 95:7544–49 [Google Scholar]
  32. Magge D, Guo ZS, O'Malley ME, Francis L, Ravindranathan R, Bartlett DL. 32.  2013. Inhibitors of C5 complement enhance vaccinia virus oncolysis. Cancer Gene Ther. 20:342–50 [Google Scholar]
  33. Smith GL, Moss B. 33.  1983. Infectious poxvirus vectors have capacity for at least 25 000 base pairs of foreign DNA. Gene 25:21–28 [Google Scholar]
  34. De Clercq E. 34.  2010. Historical perspectives in the development of antiviral agents against poxviruses. Viruses 2:1322–39 [Google Scholar]
  35. Chan WM, Rahman MM, McFadden G. 35.  2013. Oncolytic myxoma virus: the path to clinic. Vaccine 31:4252–58 [Google Scholar]
  36. Evgin L, Vaha-Koskela M, Rintoul J, Falls T, Le Boeuf F. 36.  et al. 2010. Potent oncolytic activity of raccoonpox virus in the absence of natural pathogenicity. Mol. Ther. 18:896–902 [Google Scholar]
  37. Hu Y, Lee J, McCart JA, Xu H, Moss B. 37.  et al. 2001. Yaba-like disease virus: an alternative replicating poxvirus vector for cancer gene therapy. J. Virol. 75:10300–8 [Google Scholar]
  38. Kochneva GV, Sivolobova GF, Yudina KV, Babkin IV, Chumakov PM, Netesov SV. 38.  2012. Oncolytic poxviruses. Mol. Genet. Microbiol. Virol. 27:7–15 [Google Scholar]
  39. Castrucci MR, Facchini M, Di Mario G, Garulli B, Sciaraffia E. 39.  et al. 2014. Modified vaccinia virus Ankara expressing the hemagglutinin of pandemic (H1N1) 2009 virus induces cross-protective immunity against Eurasian “avian-like” H1N1 swine viruses in mice. Influenza Other Respir. Viruses 8:367–75 [Google Scholar]
  40. Garcia-Arriaza J, Cepeda V, Hallengard D, Sorzano CO, Kummerer BM. 40.  et al. 2014. A novel poxvirus-based vaccine (MVA-CHIKV) is highly immunogenic and protects mice against chikungunya infection. J. Virol. 88:3527–47 [Google Scholar]
  41. Goepfert PA, Elizaga ML, Seaton KE, Tomaras GD, Montefiori DC. 41.  et al. 2014. Specificity and six-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J. Infect. Dis. 21099–110 [Google Scholar]
  42. Guse K, Cerullo V, Hemminki A. 42.  2011. Oncolytic vaccinia virus for the treatment of cancer. Expert Opin. Biol. Ther. 11:595–608 [Google Scholar]
  43. Kirn DH, Thorne SH. 43.  2009. Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer. Nat. Rev. Cancer 9:64–71 [Google Scholar]
  44. Lusky M, Erbs P, Foloppe J, Acres RB. 44.  2010. Oncolytic vaccinia virus: a silver bullet?. Expert Rev. Vaccines 9:1353–56 [Google Scholar]
  45. Parato KA, Breitbach CJ, Le Boeuf F, Wang J, Storbeck C. 45.  et al. 2012. The oncolytic poxvirus JX-594 selectively replicates in and destroys cancer cells driven by genetic pathways commonly activated in cancers. Mol. Ther. 20:749–58 [Google Scholar]
  46. Thorne SH. 46.  2012. Next-generation oncolytic vaccinia vectors. Methods Mol. Biol. 797:205–15 [Google Scholar]
  47. Puhlmann M, Brown CK, Gnant M, Huang J, Libutti SK. 47.  et al. 2000. Vaccinia as a vector for tumor-directed gene therapy: biodistribution of a thymidine kinase–deleted mutant. Cancer Gene Ther. 7:66–73 [Google Scholar]
  48. Buller RM, Chakrabarti S, Cooper JA, Twardzik DR, Moss B. 48.  1988. Deletion of the vaccinia virus growth factor gene reduces virus virulence. J. Virol. 62:866–74 [Google Scholar]
  49. Buller RM, Chakrabarti S, Moss B, Fredrickson T. 49.  1988. Cell proliferative response to vaccinia virus is mediated by VGF. Virology 164:182–92 [Google Scholar]
  50. McCart JA, Ward JM, Lee J, Hu Y, Alexander HR. 50.  et al. 2001. Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res. 61:8751–57 [Google Scholar]
  51. Kerr PJ. 51.  2012. Myxomatosis in Australia and Europe: a model for emerging infectious diseases. Antivir. Res. 93:387–415 [Google Scholar]
  52. Spiesschaert B, McFadden G, Hermans K, Nauwynck H, Van de Walle GR. 52.  2011. The current status and future directions of myxoma virus, a master in immune evasion. Vet. Res. 42:76 [Google Scholar]
  53. Fenner F. 53.  1959. Myxomatosis. Br. Med. Bull. 15:240–45 [Google Scholar]
  54. Kerr P, McFadden G. 54.  2002. Immune responses to myxoma virus. Viral Immunol. 15:229–46 [Google Scholar]
  55. Andrewes CH, Harisijades S. 55.  1955. Propagation of myxoma virus in one-day-old mice. Br. J. Exp. Pathol. 36:18–21 [Google Scholar]
  56. McCabe VJ, Tarpey I, Spibey N. 56.  2002. Vaccination of cats with an attenuated recombinant myxoma virus expressing feline calicivirus capsid protein. Vaccine 20:2454–62 [Google Scholar]
  57. Bartee E, McFadden G. 57.  2009. Human cancer cells have specifically lost the ability to induce the synergistic state caused by tumor necrosis factor plus interferon-β. Cytokine 47:199–205 [Google Scholar]
  58. Bartee E, Mohamed MR, Lopez MC, Baker HV, McFadden G. 58.  2009. The addition of tumor necrosis factor plus β interferon induces a novel synergistic antiviral state against poxviruses in primary human fibroblasts. J. Virol. 83:498–511 [Google Scholar]
  59. Wang G, Barrett JW, Stanford M, Werden SJ, Johnston JB. 59.  et al. 2006. Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor. Proc. Natl. Acad. Sci. USA 103:4640–45 [Google Scholar]
  60. Werden SJ, McFadden G. 60.  2008. The role of cell signaling in poxvirus tropism: the case of the M-T5 host range protein of myxoma virus. Biochim. Biophys. Acta 1784:228–37 [Google Scholar]
  61. Kim M, Williamson CT, Prudhomme J, Bebb DG, Riabowol K. 61.  et al. 2010. The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status. Oncogene 29:3990–96 [Google Scholar]
  62. Merrick AE, Ilett EJ, Melcher AA. 62.  2009. JX-594, a targeted oncolytic poxvirus for the treatment of cancer. Curr. Opin. Investig. Drugs 10:1372–82 [Google Scholar]
  63. Mastrangelo MJ, Lattime EC. 63.  2002. Virotherapy clinical trials for regional disease: in situ immune modulation using recombinant poxvirus vectors. Cancer Gene Ther. 9:1013–21 [Google Scholar]
  64. Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR. 64.  et al. 2011. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 477:99–102 [Google Scholar]
  65. Heo J, Reid T, Ruo L, Breitbach CJ, Rose S. 65.  et al. 2013. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat. Med. 19:329–36 [Google Scholar]
  66. Hwang TH, Moon A, Burke J, Ribas A, Stephenson J. 66.  et al. 2011. A mechanistic proof-of-concept clinical trial with JX-594, a targeted multi-mechanistic oncolytic poxvirus, in patients with metastatic melanoma. Mol. Ther. 19:1913–22 [Google Scholar]
  67. Park BH, Hwang T, Liu TC, Sze DY, Kim JS. 67.  et al. 2008. Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol. 9:533–42 [Google Scholar]
  68. Liu TC, Hwang T, Park BH, Bell J, Kirn DH. 68.  2008. The targeted oncolytic poxvirus JX-594 demonstrates antitumoral, antivascular, and anti-HBV activities in patients with hepatocellular carcinoma. Mol. Ther. 16:1637–42 [Google Scholar]
  69. Zhang Q, Liang C, Yu YA, Chen N, Dandekar T, Szalay AA. 69.  2009. The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5L inactivation. Mol. Genet. Genomics 282:417–35 [Google Scholar]
  70. Lun X, Ruan Y, Jayanthan A, Liu DJ, Singh A. 70.  et al. 2013. Double-deleted vaccinia virus in virotherapy for refractory and metastatic pediatric solid tumors. Mol. Oncol. 7:944–54 [Google Scholar]
  71. Lombardo Y, Scopelliti A, Cammareri P, Todaro M, Iovino F. 71.  et al. 2011. Bone morphogenetic protein 4 induces differentiation of colorectal cancer stem cells and increases their response to chemotherapy in mice. Gastroenterology 140:297–309 [Google Scholar]
  72. Piccirillo SG, Vescovi AL. 72.  2006. Bone morphogenetic proteins regulate tumorigenicity in human glioblastoma stem cells. Ernst Schering Found. Symp. Proc. 5:59–81 [Google Scholar]
  73. Duggal R, Geissinger U, Zhang Q, Aguilar J, Chen NG. 73.  et al. 2013. Vaccinia virus expressing bone morphogenetic protein-4 in novel glioblastoma orthotopic models facilitates enhanced tumor regression and long-term survival. J. Transl. Med. 11:155 [Google Scholar]
  74. Frentzen A, Yu YA, Chen N, Zhang Q, Weibel S. 74.  et al. 2009. Anti-VEGF single-chain antibody GLAF-1 encoded by oncolytic vaccinia virus significantly enhances antitumor therapy. Proc. Natl. Acad. Sci. USA 106:12915–20 [Google Scholar]
  75. Weibel S, Hofmann E, Basse-Luesebrink TC, Donat U, Seubert C. 75.  et al. 2013. Treatment of malignant effusion by oncolytic virotherapy in an experimental subcutaneous xenograft model of lung cancer. J. Transl. Med. 11:106 [Google Scholar]
  76. Hofmann E, Grummt F, Szalay AA. 76.  2011. Vaccinia virus GLV-1h237 carrying a Walker A motif mutation of mouse Cdc6 protein enhances human breast tumor therapy in mouse xenografts. Int. J. Oncol. 38:871–78 [Google Scholar]
  77. Bohlius J, Weingart O, Trelle S, Engert A. 77.  2006. Cancer-related anemia and recombinant human erythropoietin—an updated overview. Nat. Clin. Pract. Oncol. 3:152–64 [Google Scholar]
  78. Glaspy JA. 78.  2009. Erythropoietin in cancer patients. Annu. Rev. Med. 60:181–92 [Google Scholar]
  79. Henke M, Laszig R, Rube C, Schafer U, Haase KD. 79.  et al. 2003. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 362:1255–60 [Google Scholar]
  80. Leyland-Jones B, Semiglazov V, Pawlicki M, Pienkowski T, Tjulandin S. 80.  et al. 2005. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J. Clin. Oncol. 23:5960–72 [Google Scholar]
  81. Ghezzi P, Brines M. 81.  2004. Erythropoietin as an antiapoptotic, tissue-protective cytokine. Cell Death Differ. 11:Suppl. 1S37–44 [Google Scholar]
  82. Yasuda Y, Fujita Y, Matsuo T, Koinuma S, Hara S. 82.  et al. 2003. Erythropoietin regulates tumour growth of human malignancies. Carcinogenesis 24:1021–29 [Google Scholar]
  83. Hardee ME, Kirkpatrick JP, Shan S, Snyder SA, Vujaskovic Z. 83.  et al. 2005. Human recombinant erythropoietin (rEpo) has no effect on tumour growth or angiogenesis. Br. J. Cancer 93:1350–55 [Google Scholar]
  84. LaMontagne KR, Butler J, Marshall DJ, Tullai J, Gechtman Z. 84.  et al. 2006. Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor–positive breast carcinoma models. Mol. Cancer Ther. 5:347–55 [Google Scholar]
  85. Swift S, Ellison AR, Kassner P, McCaffery I, Rossi J. 85.  et al. 2010. Absence of functional EpoR expression in human tumor cell lines. Blood 115:4254–63 [Google Scholar]
  86. Nguyen DH, Chen NG, Zhang Q, Le HT, Aguilar RJ. 86.  et al. 2013. Vaccinia virus–mediated expression of human erythropoietin in tumors enhances virotherapy and alleviates cancer-related anemia in mice. Mol. Ther. 21:2054–62 [Google Scholar]
  87. Thirunavukarasu P, Sathaiah M, Gorry MC, O'Malley ME, Ravindranathan R. 87.  et al. 2013. A rationally designed A34R mutant oncolytic poxvirus: improved efficacy in peritoneal carcinomatosis. Mol. Ther. 21:1024–33 [Google Scholar]
  88. Schafer S, Weibel S, Donat U, Zhang Q, Aguilar RJ. 88.  et al. 2012. Vaccinia virus–mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors. BMC Cancer 12:366 [Google Scholar]
  89. McCart JA, Mehta N, Scollard D, Reilly RM, Carrasquillo JA. 89.  et al. 2004. Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2: molecular imaging after systemic delivery using 111In-pentetreotide. Mol. Ther. 10:553–61 [Google Scholar]
  90. Haddad D, Chen CH, Carlin S, Silberhumer G, Chen NG. 90.  et al. 2012. Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter. PLoS ONE 7:e41647 [Google Scholar]
  91. Belin LJ, Ady JW, Lewis C, Marano D, Gholami S. 91.  et al. 2013. An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma. Surgery 154:486–95 [Google Scholar]
  92. Gholami S, Chen CH, Belin LJ, Lou E, Fujisawa S. 92.  et al. 2013. Vaccinia virus GLV-1h153 is a novel agent for detection and effective local control of positive surgical margins for breast cancer. Breast Cancer Res. 15:R26 [Google Scholar]
  93. Gholami S, Haddad D, Chen CH, Chen NG, Zhang Q. 93.  et al. 2011. Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter. Surgery 150:1040–47 [Google Scholar]
  94. Haddad D, Zanzonico PB, Carlin S, Chen CH, Chen NG. 94.  et al. 2012. A vaccinia virus encoding the human sodium iodide symporter facilitates long-term image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer. J. Nucl. Med. 53:1933–42 [Google Scholar]
  95. Gholami S, Chen CH, Lou E, De Brot M, Fujisawa S. 95.  et al. 2012. Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic triple-negative breast cancer. Ann. Surg. 256:437–45 [Google Scholar]
  96. Gao J, Bernatchez C, Sharma P, Radvanyi LG, Hwu P. 96.  2013. Advances in the development of cancer immunotherapies. Trends Immunol. 34:90–98 [Google Scholar]
  97. Liu J, Wennier S, McFadden G. 97.  2010. The immunoregulatory properties of oncolytic myxoma virus and their implications in therapeutics. Microbes Infect. 12:1144–52 [Google Scholar]
  98. Rahman MM, Madlambayan GJ, Cogle CR, McFadden G. 98.  2010. Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with myxoma virus. Cytokine Growth Factor Rev. 21:169–75 [Google Scholar]
  99. Stanford MM, McFadden G. 99.  2007. Myxoma virus and oncolytic virotherapy: a new biologic weapon in the war against cancer. Expert Opin. Biol. Ther. 7:1415–25 [Google Scholar]
  100. Bartee E, Chan WM, Moreb JS, Cogle CR, McFadden G. 100.  2012. Selective purging of human multiple myeloma cells from autologous stem cell transplantation grafts using oncolytic myxoma virus. Biol. Blood Marrow Transplant. 18:1540–51 [Google Scholar]
  101. Kim M, Madlambayan GJ, Rahman MM, Smallwood SE, Meacham AM. 101.  et al. 2009. Myxoma virus targets primary human leukemic stem and progenitor cells while sparing normal hematopoietic stem and progenitor cells. Leukemia 23:2313–17 [Google Scholar]
  102. Lun X, Yang W, Alain T, Shi ZQ, Muzik H. 102.  et al. 2005. Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. Cancer Res. 65:9982–90 [Google Scholar]
  103. Fruh K, Bartee E, Gouveia K, Mansouri M. 103.  2002. Immune evasion by a novel family of viral PHD/LAP-finger proteins of gamma-2 herpesviruses and poxviruses. Virus Res. 88:55–69 [Google Scholar]
  104. Ogbomo H, Zemp FJ, Lun X, Zhang J, Stack D. 104.  et al. 2013. Myxoma virus infection promotes NK lysis of malignant gliomas in vitro and in vivo. PLoS ONE 8:e66825 [Google Scholar]
  105. Barrett JW, Cao JX, Hota-Mitchell S, McFadden G. 105.  2001. Immunomodulatory proteins of myxoma virus. Semin. Immunol. 13:73–84 [Google Scholar]
  106. Zuniga MC. 106.  2002. A pox on thee! Manipulation of the host immune system by myxoma virus and implications for viral-host co-adaptation. Virus Res. 88:17–33 [Google Scholar]
  107. Johnston JB, McFadden G. 107.  2004. Technical knockout: understanding poxvirus pathogenesis by selectively deleting viral immunomodulatory genes. Cell Microbiol. 6:695–705 [Google Scholar]
  108. Barrett JW, Alston LR, Wang F, Stanford MM, Gilbert PA. 108.  et al. 2007. Identification of host range mutants of myxoma virus with altered oncolytic potential in human glioma cells. J. Neurovirol. 13:549–60 [Google Scholar]
  109. Barrett JW, Sypula J, Wang F, Alston LR, Shao Z. 109.  et al. 2007. M135R is a novel cell surface virulence factor of myxoma virus. J. Virol. 81:106–14 [Google Scholar]
  110. Stanford MM, Shaban M, Barrett JW, Werden SJ, Gilbert PA. 110.  et al. 2008. Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo. Mol. Ther. 16:52–59 [Google Scholar]
  111. Lun X, Alain T, Zemp FJ, Zhou H, Rahman MM. 111.  et al. 2010. Myxoma virus virotherapy for glioma in immunocompetent animal models: optimizing administration routes and synergy with rapamycin. Cancer Res. 70:598–608 [Google Scholar]
  112. Irwin CR, Evans DH. 112.  2012. Modulation of the myxoma virus plaque phenotype by vaccinia virus protein F11. J. Virol. 86:7167–79 [Google Scholar]
  113. Irwin CR, Favis NA, Agopsowicz KC, Hitt MM, Evans DH. 113.  2013. Myxoma virus oncolytic efficiency can be enhanced through chemical or genetic disruption of the actin cytoskeleton. PLoS ONE 8:e84134 [Google Scholar]
  114. Bartee E, Meacham A, Wise E, Cogle CR, McFadden G. 114.  2012. Virotherapy using myxoma virus prevents lethal graft-versus-host disease following xeno-transplantation with primary human hematopoietic stem cells. PLoS ONE 7:e43298 [Google Scholar]
  115. Heo J, Breitbach CJ, Moon A, Kim CW, Patt R. 115.  et al. 2011. Sequential therapy with JX-594, a targeted oncolytic poxvirus, followed by sorafenib in hepatocellular carcinoma: preclinical and clinical demonstration of combination efficacy. Mol. Ther. 19:1170–79 [Google Scholar]
  116. Wennier ST, Liu J, Li S, Rahman MM, Mona M, McFadden G. 116.  2012. Myxoma virus sensitizes cancer cells to gemcitabine and is an effective oncolytic virotherapeutic in models of disseminated pancreatic cancer. Mol. Ther. 20:759–68 [Google Scholar]
  117. Wennier ST, Liu J, McFadden G. 117.  2012. Bugs and drugs: oncolytic virotherapy in combination with chemotherapy. Curr. Pharm. Biotechnol. 13:1817–33 [Google Scholar]
  118. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S. 118.  et al. 2009. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10:25–34 [Google Scholar]
  119. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E. 119.  et al. 2008. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359:378–90 [Google Scholar]
  120. Advani SJ, Buckel L, Chen NG, Scanderbeg DJ, Geissinger U. 120.  et al. 2012. Preferential replication of systemically delivered oncolytic vaccinia virus in focally irradiated glioma xenografts. Clin. Cancer Res. 18:2579–90 [Google Scholar]
  121. Buckel L, Advani SJ, Frentzen A, Zhang Q, Yu YA. 121.  et al. 2013. Combination of fractionated irradiation with anti-VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium. Int. J. Cancer 133:2989–99 [Google Scholar]
  122. Kyula JN, Khan AA, Mansfield D, Karapanagiotou EM, McLaughlin M. 122.  et al. 2013. Synergistic cytotoxicity of radiation and oncolytic Lister strain vaccinia in BRAF mutant melanoma depends on JNK and TNF-α signaling. Oncogene 33: 1700–12 [Google Scholar]
  123. Lun XQ, Zhou H, Alain T, Sun B, Wang L. 123.  et al. 2007. Targeting human medulloblastoma: Oncolytic virotherapy with myxoma virus is enhanced by rapamycin. Cancer Res. 67:8818–27 [Google Scholar]
  124. Seubert CM, Stritzker J, Hess M, Donat U, Sturm JB. 124.  et al. 2011. Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA. Cancer Gene Ther. 18:42–52 [Google Scholar]
  125. Sturm JB, Hess M, Weibel S, Chen NG, Yu YA. 125.  et al. 2012. Functional hyper-IL-6 from vaccinia virus–colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy. J. Transl. Med. 10:9 [Google Scholar]
  126. Thomas DL, Doty R, Tosic V, Liu J, Kranz DM. 126.  et al. 2011. Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors. Cancer Immunol. Immunother. 60:1461–72 [Google Scholar]
  127. Zemp FJ, Lun X, McKenzie BA, Zhou H, Maxwell L. 127.  et al. 2013. Treating brain tumor–initiating cells using a combination of myxoma virus and rapamycin. Neuro-Oncology 15:904–20 [Google Scholar]
  128. Stritzker J, Kirscher L, Scadeng M, Deliolanis NC, Morscher S. 128.  et al. 2013. Vaccinia virus–mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer. Proc. Natl. Acad. Sci. USA 110:3316–20 [Google Scholar]
  129. Munguia A, Ota T, Miest T, Russell SJ. 129.  2008. Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth. Gene Ther. 15:797–806 [Google Scholar]
  130. Power AT, Wang J, Falls TJ, Paterson JM, Parato KA. 130.  et al. 2007. Carrier cell–based delivery of an oncolytic virus circumvents antiviral immunity. Mol. Ther. 15:123–30 [Google Scholar]
  131. Willmon C, Harrington K, Kottke T, Prestwich R, Melcher A, Vile R. 131.  2009. Cell carriers for oncolytic viruses: Fed Ex for cancer therapy. Mol. Ther. 17:1667–76 [Google Scholar]
  132. Mader EK, Butler G, Dowdy SC, Mariani A, Knutson KL. 132.  et al. 2013. Optimizing patient derived mesenchymal stem cells as virus carriers for a phase I clinical trial in ovarian cancer. J. Transl. Med. 11:20 [Google Scholar]
  133. Josiah DT, Zhu D, Dreher F, Olson J, McFadden G, Caldas H. 133.  2010. Adipose-derived stem cells as therapeutic delivery vehicles of an oncolytic virus for glioblastoma. Mol. Ther. 18:377–85 [Google Scholar]
  134. Thorne SH, Negrin RS, Contag CH. 134.  2006. Synergistic antitumor effects of immune cell–viral biotherapy. Science 311:1780–84 [Google Scholar]
  135. Sampath P, Li J, Hou W, Chen H, Bartlett DL, Thorne SH. 135.  2013. Crosstalk between immune cell and oncolytic vaccinia therapy enhances tumor trafficking and antitumor effects. Mol. Ther. 21:620–28 [Google Scholar]
  136. Ribas A, Wolchok JD. 136.  2013. Combining cancer immunotherapy and targeted therapy. Curr. Opin. Immunol. 25:291–96 [Google Scholar]
  137. Vanneman M, Dranoff G. 137.  2012. Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer 12:237–51 [Google Scholar]
  138. Nichols AC, Yoo J, Um S, Mundi N, Palma DA. 138.  et al. 2014. Vaccinia virus outperforms a panel of other poxviruses as a potent oncolytic agent for the control of head and neck squamous cell carcinoma cell lines. Intervirology 57:17–22 [Google Scholar]
  139. Gil M, Seshadri M, Komorowski MP, Abrams SI, Kozbor D. 139.  2013. Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases. Proc. Natl. Acad. Sci. USA 110:E1291–300 [Google Scholar]
  140. Ehrig K, Kilinc MO, Chen NG, Stritzker J, Buckel L. 140.  et al. 2013. Growth inhibition of different human colorectal cancer xenografts after a single intravenous injection of oncolytic vaccinia virus GLV-1h68. J. Transl. Med. 11:79 [Google Scholar]
  141. Wang H, Chen NG, Minev BR, Szalay AA. 141.  2012. Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells. J. Transl. Med. 10:167 [Google Scholar]
  142. Gentschev I, Donat U, Hofmann E, Weibel S, Adelfinger M. 142.  et al. 2010. Regression of human prostate tumors and metastases in nude mice following treatment with the recombinant oncolytic vaccinia virus GLV-1h68. J. Biomed. Biotechnol. 2010:489759 [Google Scholar]
  143. Gentschev I, Muller M, Adelfinger M, Weibel S, Grummt F. 143.  et al. 2011. Efficient colonization and therapy of human hepatocellular carcinoma (HCC) using the oncolytic vaccinia virus strain GLV-1h68. PLoS ONE 6:e2 2069 [Google Scholar]
  144. He S, Li P, Chen CH, Bakst RL, Chernichenko N. 144.  et al. 2012. Effective oncolytic vaccinia therapy for human sarcomas. J. Surg. Res. 175:e53–60 [Google Scholar]
  145. Chernichenko N, Linkov G, Li P, Bakst RL, Chen CH. 145.  et al. 2013. Oncolytic vaccinia virus therapy of salivary gland carcinoma. JAMA Otolaryngol. Head Neck Surg. 139:173–82 [Google Scholar]
  146. Yu Z, Li S, Brader P, Chen N, Yu YA. 146.  et al. 2009. Oncolytic vaccinia therapy of squamous cell carcinoma. Mol. Cancer 8:45 [Google Scholar]
  147. Brader P, Kelly KJ, Chen N, Yu YA, Zhang Q. 147.  et al. 2009. Imaging a genetically engineered oncolytic vaccinia virus (GLV-1h99) using a human norepinephrine transporter reporter gene. Clin. Cancer Res. 15:3791–801 [Google Scholar]
  148. Chen N, Zhang Q, Yu YA, Stritzker J, Brader P. 148.  et al. 2009. A novel recombinant vaccinia virus expressing the human norepinephrine transporter retains oncolytic potential and facilitates deep-tissue imaging. Mol. Med. 15:144–51 [Google Scholar]
  149. Wu Y, Lun X, Zhou H, Wang L, Sun B. 149.  et al. 2008. Oncolytic efficacy of recombinant vesicular stomatitis virus and myxoma virus in experimental models of rhabdoid tumors. Clin. Cancer Res. 14:1218–27 [Google Scholar]
  150. Yu YA, Galanis C, Woo Y, Chen N, Zhang Q. 150.  et al. 2009. Regression of human pancreatic tumor xenografts in mice after a single systemic injection of recombinant vaccinia virus GLV-1h68. Mol. Cancer Ther. 8:141–51 [Google Scholar]

Data & Media loading...

An introduction to the topic from authors Winnie M. Chan and Grant McFadden.

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error