Skip to main content
SpringerLink
Log in

Oncolytic Viral Therapy Using Reovirus

  • Protocol
Gene Therapy of Solid Cancers

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1317))

Abstract

Current mainstays in cancer treatment such as chemotherapy, radiation therapy, hormonal manipulation, and even targeted therapies such as Trastuzumab (herceptin) for breast cancer or Iressa (gefitinib) for non-small cell lung cancer among others are limited by lack of efficacy, cellular resistance, and toxicity. Dose escalation and combination therapies designed to overcome resistance and increase efficacy are limited by a narrow therapeutic index. Oncolytic viruses are one such group of new biological therapeutics that appears to have a wide spectrum of anticancer activity with minimal human toxicity.

Since the malignant phenotype of tumors is the culmination of multiple mutations that occur in genes eventually leading to aberrant signaling pathways, oncolytic viruses either natural or engineered specifically target tumor cells taking advantage of this abnormal cellular signaling for their replication. Reovirus is one such naturally occurring double-stranded RNA virus that exploits altered signaling pathways (including Ras) in a myriad of cancers. The ability of reovirus to infect and lyse tumors under in vitro, in vivo, and ex vivo conditions has been well documented previously by us and others. The major mechanism of reovirus oncolysis of cancer cells has been shown to occur through apoptosis with autophagy taking place during this process in certain cancers. In addition, the synergistic antitumor effects of reovirus in combination with radiation or chemotherapy have also been demonstrated for reovirus resistant and moderately sensitive tumors. Recent progress in our understanding of viral immunology in the tumor microenvironment has diverted interest in exploring immunologic mechanisms to overcome resistance exhibited by chemotherapeutic drugs in cancer. Thus, currently several investigations are focusing on immune potentiating of reovirus for maximal tumor targeting. This chapter therefore has concentrated on immunologic cell death induction with reovirus as a novel approach to cancer therapy used under in vitro and in vivo conditions, as well as in a clinical setting. Reovirus phase I clinical trials have shown indications of efficacy, and several phase II/III trials are ongoing at present. Reovirus’s extensive preclinical efficacy, replication competency, and low toxicity profile in humans have placed it as an attractive anticancer therapeutic for ongoing clinical testing that are highlighted in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Butel JS (2000) Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 21(3):405–426

    Article  CAS  PubMed  Google Scholar 

  2. DePace N (1921) Sulla comparsa di un enorme cancro vegetante del collo dell'utero senza cura chirurgica. Ginecologia 9:82–89

    Google Scholar 

  3. Bluming AZ, Ziegler JL (1971) Regression of Burkitt’s lymphoma in association with measles infection. Lancet 2(7715):105–106

    Article  CAS  PubMed  Google Scholar 

  4. Taqi AM, Abdurrahman MB, Yakubu AM, Fleming AF (1981) Regression of Hodgkin’s disease after measles. Lancet 1(8229):1112

    Article  CAS  PubMed  Google Scholar 

  5. Moore AE (1954) Effects of viruses on tumors. Annu Rev Microbiol 8:393–410

    Article  CAS  PubMed  Google Scholar 

  6. Sinkovics J, Horvath J (1993) New developments in the virus therapy of cancer: a historical review. Intervirology 36(4):193–214

    CAS  PubMed  Google Scholar 

  7. Nibert M, Shiff L (2001) Reoviruses and Their Replication. In: Knipe DM, Howley PM (eds) Fields virology. Lippincott-Raven, Philadelphia, PA

    Google Scholar 

  8. Weiner HL, Fields BN (1977) Neutralization of reovirus: the gene responsible for the neutralization antigen. J Exp Med 146(5):1305–1310

    Article  CAS  PubMed  Google Scholar 

  9. Ramos-Alvarez M, Sabin AB (1954) Characteristics of poliomyelitis and other enteric viruses recovered in tissue culture from healthy American children. Proc Soc Exp Biol Med 87(3):655–661

    Article  CAS  PubMed  Google Scholar 

  10. Sabin AB (1959) Reoviruses. A new group of respiratory and enteric viruses formerly classified as ECHO type 10 is described. Science 130:1387–1389

    Article  CAS  PubMed  Google Scholar 

  11. Rosen L (1960) Serologic grouping of reoviruses by hemagglutination-inhibition. Am J Hyg 71:242–249

    CAS  PubMed  Google Scholar 

  12. Rosen L, Hovis JF, Mastrota FM, Bell JA, Huebner RJ (1960) Observations on a newly recognized virus (Abney) of the reovirus family. Am J Hyg 71:258–265

    CAS  PubMed  Google Scholar 

  13. Cashdollar LW, Chmelo RA, Wiener JR, Joklik WK (1985) Sequences of the S1 genes of the three serotypes of reovirus. Proc Natl Acad Sci U S A 82(1):24–28

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Duncan R, Horne D, Cashdollar LW, Joklik WK, Lee PW (1990) Identification of conserved domains in the cell attachment proteins of the three serotypes of reovirus. Virology 174(2):399–409

    Article  CAS  PubMed  Google Scholar 

  15. Atwater JA, Munemitsu SM, Samuel CE (1986) Biosynthesis of reovirus-specified polypeptides. Molecular cDNA cloning and nucleotide sequence of the reovirus serotype 1 Lang strain s4 mRNA which encodes the major capsid surface polypeptide sigma 3. Biochem Biophys Res Commun 136(1):183–192

    Article  CAS  PubMed  Google Scholar 

  16. Tarlow O, McCorquodale JG, McCrae MA (1988) Molecular cloning and sequencing of the gene (M2) encoding the major virion structural protein (mu 1-mu 1C) of serotypes 1 and 3 of mammalian reovirus. Virology 164(1):141–146

    Article  CAS  PubMed  Google Scholar 

  17. Dermody TS, Schiff LA, Nibert ML, Coombs KM, Fields BN (1991) The S2 gene nucleotide sequences of prototype strains of the three reovirus serotypes: characterization of reovirus core protein sigma 2. J Virol 65(11):5721–5731

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Zou S, Brown EG (1992) Nucleotide sequence comparison of the M1 genome segment of reovirus type 1 Lang and type 3 dearing. Virus Res 22(2):159–164

    Article  CAS  PubMed  Google Scholar 

  19. Stanley NF, Dorman DC, Ponsford J (1953) Studies on the pathogenesis of a hitherto undescribed virus (hepato-encephalomyelitis) producing unusual symptoms in suckling mice. Aust J Exp Biol Med Sci 31(2):147–159

    Google Scholar 

  20. Saito T, Shinozaki K, Matsunaga T et al (2004) Lack of evidence for reovirus infection in tissues from patients with biliary atresia and congenital dilatation of the bile duct. J Hepatol 40(2):203–211

    Article  PubMed  Google Scholar 

  21. Loken SD, Norman K, Hirasawa K, Nodwell M, Lester WM, Demetrick DJ (2004) Morbidity in immunosuppressed (SCID/NOD) mice treated with reovirus (dearing 3) as an anti-cancer biotherapeutic. Cancer Biol Ther 3(8):734–738

    Article  CAS  PubMed  Google Scholar 

  22. Hirasawa K, Nishikawa SG, Norman KL, Alain T, Kossakowska A, Lee PW (2002) Oncolytic reovirus against ovarian and colon cancer. Cancer Res 62(6):1696–1701

    CAS  PubMed  Google Scholar 

  23. Rosen L, Evans HE, Spickard A (1963) Reovirus infections in human volunteers. Am J Hyg 77:29–37

    Google Scholar 

  24. Johansson PJ, Sveger T, Ahlfors K, Ekstrand J, Svensson L (1996) Reovirus type 1 associated with meningitis. Scand J Infect Dis 28(2):117–120

    Article  CAS  PubMed  Google Scholar 

  25. Joske RA, Keall DD, Leak PJ, Stanley NF, Walters MN (1964) Hepatitis-encephalitis in humans with reovirus infection. Arch Intern Med 113:811–816

    Article  CAS  PubMed  Google Scholar 

  26. Strong JE, Tang D, Lee PW (1993) Evidence that the epidermal growth factor receptor on host cells confers reovirus infection efficiency. Virology 197(1):405–411

    Article  CAS  PubMed  Google Scholar 

  27. Tang D, Strong JE, Lee PW (1993) Recognition of the epidermal growth factor receptor by reovirus. Virology 197(1):412–414

    Article  CAS  PubMed  Google Scholar 

  28. Strong JE, Lee PW (1996) The v-erbB oncogene confers enhanced cellular susceptibility to reovirus infection. J Virol 70(1):612–616

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Campbell SL, Khosravi-Far R, Rossman KL, Clark GJ, Der CJ (1998) Increasing complexity of Ras signaling. Oncogene 17(11 Reviews):1395–1413

    Article  CAS  PubMed  Google Scholar 

  30. Bianco R, Melisi D, Ciardiello F, Tortora G (2006) Key cancer cell signal transduction pathways as therapeutic targets. Eur J Cancer 42(3):290–294

    Article  CAS  PubMed  Google Scholar 

  31. Strong JE, Coffey MC, Tang D, Sabinin P, Lee PW (1998) The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO J 17(12):3351–3362

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Mundschau LJ, Faller DV (1992) Oncogenic ras induces an inhibitor of double-stranded RNA-dependent eukaryotic initiation factor 2 alpha-kinase activation. J Biol Chem 267(32):23092–23098

    CAS  PubMed  Google Scholar 

  33. Mundschau LJ, Faller DV (1994) Endogenous inhibitors of the dsRNA-dependent eIF-2 alpha protein kinase PKR in normal and ras-transformed cells. Biochimie 76(8):792–800

    Article  CAS  PubMed  Google Scholar 

  34. Bischoff JR, Samuel CE (1989) Mechanism of interferon action. Activation of the human P1/eIF-2 alpha protein kinase by individual reovirus s-class mRNAs: s1 mRNA is a potent activator relative to s4 mRNA. Virology 172(1):106–115

    Article  CAS  PubMed  Google Scholar 

  35. Panniers R, Henshaw EC (1983) A GDP/GTP exchange factor essential for eukaryotic initiation factor 2 cycling in Ehrlich ascites tumor cells and its regulation by eukaryotic initiation factor 2 phosphorylation. J Biol Chem 258(13):7928–7934

    CAS  PubMed  Google Scholar 

  36. Norman KL, Hirasawa K, Yang AD, Shields MA, Lee PW (2004) Reovirus oncolysis: the Ras/RalGEF/p38 pathway dictates host cell permissiveness to reovirus infection. Proc Natl Acad Sci U S A 101(30):11099–11104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Hashiro G, Loh PC, Yau JT (1977) The preferential cytotoxicity of reovirus for certain transformed cell lines. Arch Virol 54(4):307–315

    Article  CAS  PubMed  Google Scholar 

  38. Duncan MR, Stanish SM, Cox DC (1978) Differential sensitivity of normal and transformed human cells to reovirus infection. J Virol 28(2):444–449

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Coffey MC, Strong JE, Forsyth PA, Lee PW (1998) Reovirus therapy of tumors with activated Ras pathway. Science 282(5392):1332–1334

    Article  CAS  PubMed  Google Scholar 

  40. Connolly JL, Rodgers SE, Clarke P et al (2000) Reovirus-induced apoptosis requires activation of transcription factor NF-kappaB. J Virol 74(7):2981–2989

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Clarke P, Meintzer SM, Spalding AC, Johnson GL, Tyler KL (2001) Caspase 8-dependent sensitization of cancer cells to TRAIL-induced apoptosis following reovirus-infection. Oncogene 20(47):6910–6919

    Article  CAS  PubMed  Google Scholar 

  42. Clarke P, Tyler KL (2007) Down-regulation of cFLIP following reovirus infection sensitizes human ovarian cancer cells to TRAIL-induced apoptosis. Apoptosis 12(1):211–223

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Smakman N, van den Wollenberg DJ, Elias SG et al (2006) KRAS(D13) Promotes apoptosis of human colorectal tumor cells by ReovirusT3D and oxaliplatin but not by tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 66(10):5403–5408

    Article  CAS  PubMed  Google Scholar 

  44. Thirukkumaran C, Shi ZH, Spurrell J, Thirukkumaran P, Morris D (2007) Breast cancer oncolysis by reovirus is mediated through upregulation of PUMA and NF-kB proteins of the apoptotic signalling pathway [abstract]. In: Proceedings of the 98th annual meeting of the american association for cancer research, AACR 2007, 48, Abstract nr. 1929

    Google Scholar 

  45. Thirukkumaran C, Thirukkumaran P, Morris D (2005) Gene expression profiling of reovirus oncolysis in breast cancer [abstract]. In: Proceedings of the 96th annual meeting of the american association for cancer research, AACR, 2005, 46, Abstract nr. 24

    Google Scholar 

  46. Mercato P, Shmulevitz M, Pan D, Stoltz D, Lee PWK (2007) Ras transformation mediates reovirus oncolysis by enhancing virus uncoating, particle infectivity and apoptosis-dependent release. Mol Ther 15:1522–3010, 1038/sj.mt.6300179

    Article  CAS  Google Scholar 

  47. Errington F, White CL, Twigger KR, Rose A, Scott K, Steele L et al (2008) Inflammatory tumour cell killing by oncolytic reovirus for the treatment of melanoma. Gene Ther 15:1257–7010

    Article  CAS  PubMed  Google Scholar 

  48. Gong J, Mita MM (2014) Activated ras signaling pathways and reovirus oncolysis: an update on the mechanism of preferential reovirus replication in cancer cells. Front Oncol 4:167. doi:10.3389/fonc.2014.00167. eCollection 2014

    PubMed Central  PubMed  Google Scholar 

  49. Thirukkumaran CM, Nodwell MJ, Hirasawa K, Shi ZQ, Diaz R, Luider J, Johnston RN, Forsyth PA, Magliocco AM, Lee P, Nishikawa S, Donnelly B, Coffey M, Trpkov K, Fonseca K, Spurrell J, Morris DG (2010) Oncolytic viral therapy for prostate cancer: efficacy of reovirus as a biological therapeutic. Cancer Res 70(6):2435–2444

    Article  CAS  PubMed  Google Scholar 

  50. Sborov DW, Nuovo G, Stiff A, Mace T, Lesinski G, Benson DM, Yvonne A, Efebera YA, Rosko AE, Pichiorri F, Hofmeiste CC (2013) A phase I trial of reolysin alone in patients with refractory or relapsed multiple myeloma. American Society of Hematology (ASH) 55th annual meeting, New Orleans, LA, 7–10 Dec 2013. Annual meeting abstract 3208

    Google Scholar 

  51. Pan D, Pan L-Z, Hill R, Marcato P, Shmulevitz M, Vassilev LT et al (2011) Stabilisation of p53 enhances reovirus-induced apoptosis and virus spread through p53-dependent NF-κB activation. Br J Cancer 105:1012–2210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Danthi P, Pruijssers AJ, Berger AK, Holm GH, Zinkel SS, Dermody TS (2010) Bid regulates the pathogenesis of neurotropic reovirus. PLoS Pathog 6:e1000980

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. Clarke P, Meintzer SM, Wang Y, Moffitt LA, Richardson-Burns SM, Johnson GL et al (2004) JNK regulates the release of proapoptotic mitochondrial factors in reovirus-infected cells. J Virol 78(23):13132–13138

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Thirukkumaran C, Shi ZQ, Luider J, Morris D (2011) Multiple myeloma oncolysis by reovirus is mediated through apoptosis via downregulation of Akt signalling and simultaneous activation of Caspase 3. In: American Association for Cancer Research (AACR) meeting proceedings, vol 52

    Google Scholar 

  55. Cho IR, Koh SS, Min HJ, Park EH, Srisuttee R, Jhun BH et al (2010) Reovirus infection induces apoptosis of TRAIL-resistant gastric cancer cells by down-regulation of akt activation. Int J Oncol 36:1023–1103

    Article  CAS  PubMed  Google Scholar 

  56. Nuovo GJ, Garofalo M, Valeri N, Roulstone V, Volinia S, Cohn DE et al (2012) Reovirus-associated reduction of microRNA-let-7d is related to the increased apoptotic death of cancer cells in clinical samples. Mod Pathol 25:1333–4410

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Thirukkumaran CM, Shi ZQ, Luider J, Kopciuk K, Gao H, Bahlis N et al (2012) Reovirus as a viable therapeutic option for the treatment of multiple myeloma. Clin Cancer Res 18:4962–4972

    Article  CAS  PubMed  Google Scholar 

  58. Thirukkumaran CM, Shi ZQ, Luider J, Kopciuk K, Gao H, Bahlis N et al (2013) Reovirus modulates autophagy during oncolysis of multiple myeloma. Autophagy 9:410–413

    Article  CAS  Google Scholar 

  59. Chiu HC, Richart S, Lin FY, Hsu WL, Liu HJ (2014) The interplay of reovirus with autophagy. Biomed Res Int 2014:8.10

    Google Scholar 

  60. Meng S, Jiang K, Zhang X, Zhang M, Zhou Z, Hu M et al (2012) Avian reovirus triggers autophagy in primary chicken fibroblast cells and vero cells to promote virus production. Arch Virol 157:661–668

    Article  CAS  PubMed  Google Scholar 

  61. Qin L, Wang Z, Tao L, Wang Y (2010) ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy 6:239–247

    Article  CAS  PubMed  Google Scholar 

  62. Kelly KR, Espitia CM, Mahalingam D, Oyajobi BO, Coffey M, Giles FJ et al (2012) Reovirus therapy stimulates endoplasmic reticular stress, Noxa induction, and augments bortezomib-mediated apoptosis in multiple myeloma. Oncogene 31:3023–3810

    Article  CAS  PubMed  Google Scholar 

  63. Berger AK, Danthi P (2013) Reovirus activates a caspase-independent cell death pathway. MBio 4:e00178-13

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  64. Ikeda Y, Nishimura G, Yanoma S, Kubota A, Furukawa M, Tsukuda M (2004) Reovirus oncolysis in human head and neck squamous carcinoma cells. Auris Nasus Larynx 31:407–1210

    Article  PubMed  Google Scholar 

  65. Yuan J, Kroemer G (2010) Alternative cell death mechanisms in development and beyond. Genes Dev 24:2592–60210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Wu W, Liu P, Li J (2012) Necroptosis: an emerging form of programmed cell death. Crit Rev Oncol Hematol 82:249–5810

    Article  PubMed  Google Scholar 

  67. Thirukkumaran CM, Morris D (2009) Virotherapy with reovirus. In: Gene therapy of cancer. Methods in molecular medicine. The Humana Press, Totowa, NJ

    Google Scholar 

  68. Maitra R, Ghalib MH, Goel S (2012) Reovirus: a targeted therapeutic—progress and potential. Mol Cancer Res 10(12):1514–1525

    Article  CAS  PubMed  Google Scholar 

  69. Kyula JN, Roulstone V, Karapanagiotou EM, Melcher AA, Harrington KJ (2012) Oncolytic reovirus type 3 (Dearing) as a novel therapy in head and neck cancer. Expert Opin Biol Ther 12(12):1669–1678

    Article  CAS  PubMed  Google Scholar 

  70. Russell SJ, Peng KW, Bell JC (2012) Oncolytic virotherapy. Nat Biotechnol 30(7):658–670

    Article  CAS  PubMed  Google Scholar 

  71. Patel MR, Kratzke RA (2013) Oncolytic virus therapy for cancer: the first wave of translational clinical trials. Transl Res 161(4):355–364

    Article  CAS  PubMed  Google Scholar 

  72. Guo ZS, Thorne SH, Bartlett DL (2008) Oncolytic virotherapy: molecular targets in tumor-selective replication and carrier cell-mediated delivery of oncolytic viruses. Biochim Biophys Acta 1785(2):217–231

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Guo ZS, Liu Z, Bartlett DL (2014) Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity. Front Oncol 4:74

    PubMed Central  PubMed  Google Scholar 

  74. Prestwich RJ, Errington F, Diaz RM, Pandha HS, Harrington KJ, Melcher AA, Vile RG (2009) The case of oncolytic viruses versus the immune system: waiting on the judgment of Solomon. Hum Gene Ther 20(10):1119–1132

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T (2014) Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 14(2):135–146

    Article  CAS  PubMed  Google Scholar 

  76. Kalos M, June CH (2013) Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity 39(1):49–60

    Article  CAS  PubMed  Google Scholar 

  77. Kershaw MH, Westwood JA, Darcy PK (2013) Gene-engineered T cells for cancer therapy. Nat Rev Cancer 13(8):525–541

    Article  CAS  PubMed  Google Scholar 

  78. Restifo NP, Dudley ME, Rosenberg SA (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 12(4):269–281

    Article  CAS  PubMed  Google Scholar 

  79. McKee MD, Fichera A, Nishimura MI (2007) T cell immunotherapy. Front Biosci 12:919–932

    Article  CAS  PubMed  Google Scholar 

  80. Hanada K, Restifo NP (2013) Double or nothing on cancer immunotherapy. Nat Biotechnol 31(1):33–41

    Article  CAS  PubMed  Google Scholar 

  81. Couzin-Frankel J (2013) The dizzying journey to a new cancer arsenal. Science 340(6140):1514–1518

    Article  CAS  PubMed  Google Scholar 

  82. Prestwich RJ, Ilett EJ, Errington F, Diaz RM, Steele LP, Kottke T, Thompson J, Galivo F, Harrington KJ, Pandha HS, Selby PJ, Vile RG, Melcher AA (2009) Immune-mediated antitumor activity of reovirus is required for therapy and is independent of direct viral oncolysis and replication. Clin Cancer Res 15(13):4374–4381

    Article  CAS  PubMed  Google Scholar 

  83. Janeway C (1989) Immunogenicity signals 1,2,3 … and 0. Immunol Today 10(9):283–286

    Article  CAS  PubMed  Google Scholar 

  84. Janeway CA (1989) Approaching the asymptote? Evolution and revolution in Immunology. Cold Spring Harb Symp Quant Biol 54(1):1–13

    Article  CAS  PubMed  Google Scholar 

  85. Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12(1):991–1045

    Article  CAS  PubMed  Google Scholar 

  86. Zitvogel L, Tesniere A, Kroemer G (2006) Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6:715

    Article  CAS  PubMed  Google Scholar 

  87. Sznol M, Cheng L (2013) Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res 19(5):1021–1034

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Leung AM, Lee AF, Ozao-Choy J, Ramos RI, Hamid O, O’Day SJ, Shin-Sim M, Morton DL, Faries MB, Sieling PA, Lee DJ (2014) Clinical benefit from Ipilimumab therapy in melanoma patients may be associated with serum CTLA4 levels. Front Oncol 4:110. doi:10.3389/fonc.2014.00110. eCollection 2014

    PubMed Central  PubMed  Google Scholar 

  89. Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Placentini M, Zitvogel L, Kroemer G, Larochette N, van Endert P, Ciccosanti F (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13(1):54–61

    Article  CAS  PubMed  Google Scholar 

  90. Tesniere A, Apetoh L, Ghiringhelli F, Joza N, Panaretakis T, Kepp O, Schlemmer F, Zitvogel L, Kroemer G (2008) Immunogenic cancer cell death: a key-lock paradigm. Curr Opin Immunol 20(5):504–511

    Article  CAS  PubMed  Google Scholar 

  91. Green DR, Ferguson T, Zitvogel L, Kroemer G (2009) Immunogenic and tolerogenic cell death. Nat Rev Immunol 9(5):353–363

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Bartlett DL, Liu Z, Sathaiah M, Ravindranathan R, Guo Z, He Y (2013) Oncolytic viruses as therapeutic cancer vaccines. Mol Cancer 12:103

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Inoue H, Tani K (2014) Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments. Cell Death Differ 21(1):39–49

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Tesniere A, Panaretakis T, Kepp O, Apetoh L, Ghiringhelli F, Zitvogel L, Kroemer G (2008) Molecular characteristics of immunogenic cancer cell death. Cell Death Differ 15(1):3–12

    Article  CAS  PubMed  Google Scholar 

  95. Endo Y, Sakai R, Ouchi M, Onimatsu H, Hioki M, Kagawa S et al (2008) Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation. Oncogene 27:2375–8110

    Article  CAS  PubMed  Google Scholar 

  96. Guo ZS, Naik A, O’Malley ME, Popovic P, Demarco R, Hu Y et al (2005) The enhanced tumor selectivity of an oncolytic vaccinia lacking the host range and antiapoptosis genes SPI-1 and SPI-2. Cancer Res 65:9991–9998

    Article  CAS  PubMed  Google Scholar 

  97. Liikanen I, Ahtiainen L, Hirvinen ML, Bramante S, Cerullo V, Nokisalmi P et al (2013) Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients. Mol Ther 21:1212–2310

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Gujar SA, Pan DA, Marcato P, Garant KA, Lee PW (2011) Oncolytic virus-initiated protective immunity against prostate cancer. Mol Ther 19(4):797–804

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Gujar S, Dielschneider R, Clements D, Helson E, Shmulevitz M, Marcato P, Pan D, Pan LZ, Ahn DG, Alawadhi A, Lee PW (2013) Multifaceted therapeutic targeting of ovarian peritoneal carcinomatosis through virus-induced immunomodulation. Mol Ther 21(2):338–347

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Casares N, Pequignot MO, Tesniere A, Ghiringhelli F, Roux S, Chaput N, Schmitt E, Hamai A, Hervas-Stubbs S, Obeid M, Coutant F, Metivier D, Pichard E, Aucouturier P, Pierron G, Garrido C, Zitvogel L, Kroemer G (2005) Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med 202(12):1691–1701

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira JP, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, Andre F, Delaloge S, Tursz T, Kroemer G, Zitvogel L (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13(9):1050–1059

    Article  CAS  PubMed  Google Scholar 

  102. Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED, Carbone DP, Gabrilovich DI (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6(5):1755–1766

    CAS  PubMed  Google Scholar 

  103. Vicari AP, Caux C, Trinchieri G (2002) Tumour escape from immune surveillance through dendritic cell inactivation. Semin Cancer Biol 12(1):33–42

    Article  CAS  PubMed  Google Scholar 

  104. Perrot I, Blanchard D, Freymond N, Isaac S, Guibert B, Pacheco Y, Lebecque S (2007) Dendritic cells infiltrating human non-small cell lung cancer are blocked at immature stage. J Immunol 178(5):2763–2769

    Article  CAS  PubMed  Google Scholar 

  105. Pichlmair A, Reis e Sousa C (2007) Innate recognition of viruses. Immunity 27(3):370–383

    Article  CAS  PubMed  Google Scholar 

  106. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, Reis e Sousa C (2006) RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314(5801):997–1001

    Article  CAS  PubMed  Google Scholar 

  107. Errington F, Steele L, Prestwich R, Harrington KJ, Pandha HS, Vidal L, De Bono J, Selby P, Coffey M, Vile R, Melcher A (2008) Reovirus activates human dendritic cells to promote innate antitumor immunity. J Immunol 180(9):6018–6026

    Article  CAS  PubMed  Google Scholar 

  108. Morris DG, Feng X, DiFrancesco LM, Fonseca K, Forsyth PA, Paterson AH, Coffey MC, Thompson B (2013) REO-001: a phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin®) in patients with advanced solid tumors. Invest New Drugs 31(3):696–706

    Article  CAS  PubMed  Google Scholar 

  109. Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Che X, Iwashige H, Aridome K, Hokita S, Aikou T (2000) Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer 88(3):577–583

    Article  CAS  PubMed  Google Scholar 

  110. Takanami I, Takeuchi K, Giga M (2001) The prognostic value of natural killer cell infiltration in resected pulmonary adenocarcinoma. J Thorac Cardiovasc Surg 121(6):1058–1063

    Article  CAS  PubMed  Google Scholar 

  111. Villegas FR, Coca S, Villarrubia VG, Jimenez R, Chillon MJ, Jareno J, Zuil M, Callol L (2002) Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer 35(1):23–28

    Article  PubMed  Google Scholar 

  112. Ghiringhelli F, Apetoh L, Housseau F, Kroemer G, Zitvogel L (2007) Links between innate and cognate tumor immunity. Curr Opin Immunol 19(2):224–231

    Article  CAS  PubMed  Google Scholar 

  113. Waldhauer I, Steinle A (2008) NK cells and cancer immunosurveillance. Oncogene 27(45):5932–5943

    Article  CAS  PubMed  Google Scholar 

  114. Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter M, Perricaudet M, Tursz T, Maraskovsky E, Zitvogel L (1999) Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5(4):405–411

    Article  CAS  PubMed  Google Scholar 

  115. Reschner A, Hubert P, Delvenne P, Boniver J, Jacobs N (2008) Innate lymphocyte and dendritic cell cross-talk: a key factor in the regulation of the immune response. Clin Exp Immunol 152(2):219–226

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  116. Prestwich RJ, Errington F, Steele LP, Ilert EJ, Morgan RS, Harrington KJ, Pandha SH, Selby PJ, Vile RG, Melcher AA (2009) Reciprocal human dendritic cell–natural killer cell interactions induce antitumor activity following tumor cell infection by oncolytic reovirus. J Immunol 183:4312–4321

    Article  CAS  PubMed  Google Scholar 

  117. Steele L, Errington F, Prestwich R, Ilett E, Harrington K, Pandha H, Coffey M, Selby P, Vile R, Melcher A (2011) Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-κB mediated and supports innate and adaptive anti-tumour immune priming. Mol Cancer 10:20

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  118. Bracci L, Moschella F, Sestili P, La Sorsa V, Valentini M, Canini I, Baccarini S, Maccari S, Ramoni C, Belardelli F, Proietti E (2007) Cyclophosphamide enhances the antitumor efficacy of adoptively transferred immune cells through the induction of cytokine expression, B-cell and T-cell homeostatic proliferation, and specific tumor infiltration. Clin Cancer Res 13(2):644–653

    Article  CAS  PubMed  Google Scholar 

  119. Lichty BD, Power AT, Stojdl DF, Bell JC (2004) Vesicular stomatitis virus: re-inventing the bullet. Trends Mol Med 10(5):210–216

    Article  CAS  PubMed  Google Scholar 

  120. Brentjens RJ, Rivière I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O, Olszewska M, Bernal Y, Pegram H, Przybylowski M, Hollyman D, Usachenko Y, Pirraglia D, Hosey J, Santos E, Halton E, Maslak P, Scheinberg D, Jurcic J, Heaney M, Heller G, Frattini M, Sadelain M (2011) Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 118(18):4817–4828

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  121. Hirasawa K, Nishikawa SG, Norman KL, Coffey MC, Thompson BG, Yoon CS, Waisman DM, Lee PW (2003) Systemic reovirus therapy of metastatic cancer in immune-competent mice. Cancer Res 63(2):348–353

    CAS  PubMed  Google Scholar 

  122. Smakman N, Van Der Bilt JD, Van Den Wollenberg DJ, Hoeben RC, Borel Rinkes IH, Kranenburg O (2006) Immunosuppression promotes reovirus therapy of colorectal liver metastases. Cancer Gene Ther 13(8):815–818

    Article  CAS  PubMed  Google Scholar 

  123. Qiao J, Wang H, Kottke T, White C, Twigger K, Diaz RM, Thompson J, Selby P, De Bono J, Melcher A, Pandha H, Coffey M, Vile R, Harrington K (2008) Cyclophosphamide facilitates antitumor efficacy against subcutaneous tumors following intravenous delivery of reovirus. Clin Cancer Res 14(1):259–269

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  124. Schulz O, Diebold SS, Chen M, Naslund TI, Nolte MA, Alexopoulou L, Azuma YT, Flavell RA, Liljestrom P, Reis e Sousa C (2005) Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 433(7028):887–892

    Article  CAS  PubMed  Google Scholar 

  125. Prestwich RJ, Errington F, Ilett EJ, Morgan RS, Scott KJ, Kottke T, Thompson J, Morrison EE, Harrington KJ, Pandha HS, Selby PJ, Vile RG, Melcher AA (2008) Tumor infection by oncolytic reovirus primes adaptive antitumor immunity. Clin Cancer Res 14(22):7358–7366

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  126. Ostrand-Rosenberg S, Sinha P, Beury DW, Clements VK (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22(4):275–281

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  127. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12(4):253–268

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Greten TF, Manns MP, Korangy F (2011) Myeloid derived suppressor cells in human diseases. Int Immunopharmacol 11(7):802–807

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  129. Sun M, Lughezzani G, Perrotte P, Karakiewicz PI (2010) Treatment of metastatic renal cell carcinoma. Nat Rev Urol 7(6):327–338

    Article  CAS  PubMed  Google Scholar 

  130. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman P, Wood L, Garcia J, Dreicer R, Bukowski R, Finke J (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15(6):2148–2157

    Article  CAS  PubMed  Google Scholar 

  131. Sulkes A (2010) Novel multitargeted anticancer oral therapies: sunitinib and sorafenib as a paradigm. Isr Med Assoc J 12(10):628–632

    PubMed  Google Scholar 

  132. Ozao-Choy J, Ma G, Kao J, Wang GX, Meseck M, Sung M, Schwartz M, Divino CM, Pan PY, Chen SH (2009) The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res 69(6):2514–2522

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  133. Finke JH, Ireland J, Wood L, Bukowski R, Rayman P (2008) Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res 14(20):6674–6682

    Article  CAS  PubMed  Google Scholar 

  134. Umansky V, Sevko A (2012) Melanoma-induced immunosuppression and its neutralization. Semin Cancer Biol 22(4):319–326

    Article  CAS  PubMed  Google Scholar 

  135. Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM (2005) Gemcitabine selectively eliminates splenic Gr-1+/CD11b + myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 11(18):6713–6721

    Article  CAS  PubMed  Google Scholar 

  136. Gujar SA, Clements D, Lee PW (2014) Two is better than one: complementing oncolytic virotherapy with gemcitabine to potentiate antitumor immune responses. Oncoimmunology 3(1):e27622

    Article  PubMed Central  PubMed  Google Scholar 

  137. Pardoll DM (2012) Immunology beats cancer: a blueprint for successful translation. Nat Immunol 13(12):1129–1132

    Article  CAS  PubMed  Google Scholar 

  138. Chen LD, Flies DB (2013) Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 13(4):227–242

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  139. Mokyr MB, Kalinichenko T, Gorelik L, Bluestone JA (1998) Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice. Cancer Res 58(23):5301–5304

    CAS  PubMed  Google Scholar 

  140. van Elsas A, Hurwitz AA, Allison JP (1999) Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med 190(3):355–366

    Article  PubMed Central  PubMed  Google Scholar 

  141. Waitz R, Solomon SB, Petre EN, Trumble AE, Fassò M, Norton L, Allison JP (2012) Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy. Cancer Res 72(2):430–439

    Article  CAS  PubMed  Google Scholar 

  142. Strome SE, Dong H, Tamura H, Voss SG, Flies DB, Tamada K, Salomao D, Cheville J, Hirano F, Lin W, Kasperbauer JL, Ballman KV, Chen L (2003) B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res 63(19):6501–6505

    CAS  PubMed  Google Scholar 

  143. Hurwitz AA, Foster BA, Kwon ED, Truong T, Choi EM, Greenberg NM, Burg MB, Allison JP (2000) Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res 60(9):2444–2448

    CAS  PubMed  Google Scholar 

  144. Demaria S, Kawashima N, Yang AM, Devitt ML, Babb JS, Allison JP, Formenti SC (2005) Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res 11(2):728–734

    CAS  PubMed  Google Scholar 

  145. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S (2009) Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res 17:5379–5388

    Article  CAS  Google Scholar 

  146. Hurwitz AA, Yu TF, Leach DR, Allison JP (1998) CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc Natl Acad Sci U S A 95(17):10067–10071

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  147. Gangadhar TC, Vonderheide RH (2014) Mitigating the toxic effects of anticancer immunotherapy. Nat Rev Clin Oncol 11(2):91–99

    Article  CAS  PubMed  Google Scholar 

  148. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  149. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL (2010) Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 28(19):3167–3175

    Article  CAS  PubMed  Google Scholar 

  150. Chiocca EA (2008) The host response to cancer virotherapy. Curr Opin Mol Ther 10(1):38–45

    PubMed  Google Scholar 

  151. www.oncolyticsbiotech.ca

  152. Melcher A, Parato K, Rooney CM, Bell JC (2011) Thunder and lightning: immunotherapy and oncolytic viruses collide. Mol Ther 19(6):1008–1016

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  153. Breitbach CJ, Paterson JM, Lemay CG, Falls TJ, McGuire A, Parato KA, Stojdl DF, Daneshmand M, Speth K, Kirn D, McCart JA, Atkins H, Bell JC (2007) Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol Ther 15(9):1686–1693

    Article  CAS  PubMed  Google Scholar 

  154. Bridle BW, Hanson S, Lichty BD (2010) Combining oncolytic virotherapy and tumour vaccination. Cytokine Growth Factor Rev 21(2):143–148

    Article  CAS  PubMed  Google Scholar 

  155. Gujar SA, Marcato P, Pan D, Lee PW (2010) Reovirus virotherapy overrides tumor antigen presentation evasion and promotes protective antitumor immunity. Mol Cancer Ther 9(11):2924–2933

    Article  CAS  PubMed  Google Scholar 

  156. White CL, Twigger KR, Vidal L, De Bono JS, Coffey M, Heinemann L, Morgan R, Merrick A, Errington F, Vile RG, Melcher AA, Pandha HS, Harrington KJ (2008) Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial. Gene Ther 15(12):911–920

    Article  CAS  PubMed  Google Scholar 

  157. Forsyth P, Roldan G, George D, Wallace C, Palmer CA, Morris D et al (2008) A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas. Mol Ther 16:627–632

    Article  CAS  PubMed  Google Scholar 

  158. Kicielinski KP, Chiocca EA, Yu JS, Gill GM, Coffey M, Markert JM (2014) Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther 22:1056–1062

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  159. Vidal L, Pandha H, Yup A et al (2008) A phase I study of reolysin given intravenously to patients with advanced malignancies. Clin Cancer Res 14:7127–7137

    Article  CAS  PubMed  Google Scholar 

  160. Gollamudi R, Ghalib MH, Desai KK, Chaudhary I, Wong B, Einstein M et al (2010) Intravenous administration of Reolysin, a live replication competent RNA virus is safe in patients with advanced solid tumors. Invest New Drugs 28:641–649

    Article  PubMed  Google Scholar 

  161. Adair RA, Roulstone V, Scott KJ, Morgan R, Nuovo GJ, Fuller M et al (2012) Cell carriage, delivery, and selective replication of an oncolytic virus in tumor in patients. Sci Transl Med 4:138ra77

    PubMed Central  PubMed  Google Scholar 

  162. Galanis E, Markovic SN, Suman VJ, Nuovo GJ, Vile RG, Kottke TJ et al (2012) Phase II trial of intravenous administration of Reolysin((R)) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma. Mol Ther 20:1998–2003

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  163. Cengel KA, Voong KR, Chandrasekaran S, Maggiorella L, Brunner TB, Stanbridge E et al (2007) Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells 1. Neoplasia 9:341–348

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  164. Twigger K, Vidal L, White CL, De Bono JS, Bhide S, Coffey M, Thompson B, Vile RG, Heinemann L, Pandha HS, Errington F, Melcher AA, Harrington KJ (2008) Enhanced in vitro and in vivo cytotoxicity of combined reovirus and radiotherapy. Clin Cancer Res 14(3):912–923

    Article  CAS  PubMed  Google Scholar 

  165. Harrington KJ, Vile RG, Melcher A, Chester J, Pandha HS (2010) Clinical trials with oncolytic reovirus: moving beyond phase I into combinations with standard therapeutics. Cytokine Growth Factor Rev 21:91–98

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  166. Harrington KJ, Karapanagiotou EM, Roulstone V, Twigger KR, White CL, Vidal L et al (2010) Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers. Clin Cancer Res 16:3067–3077

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  167. Saunders M, Anthony A, Coffey M et al (2009) Results of a phase II study to evaluate the biological effects on intratumoral (ITu) reolysin in combination with low dose radiotherapy (RT) in patients (Pts) with advanced cancers. J Clin Oncol 27(Suppl):Abstract ei4514

    Google Scholar 

  168. Gujar SA, Clements D, Dielschneider R, Helson E, Marcato P, Lee PW (2014) Gemcitabine enhances the efficacy of reovirus-based oncotherapy through anti-tumour immunological mechanisms. Br J Cancer 110:83–93

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  169. Heinemann L, Simpson GR, Boxall A, Kottke T, Relph KL, Vile R et al (2011) Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer. BMC Cancer 11:221

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  170. Pandha HS, Heinemann L, Simpson GR, Melcher A, Prestwich R, Errington F, Coffey M, Harrington KJ, Morgan R (2009) Synergistic effects of oncolytic reovirus and cisplatin chemotherapy in murine malignant melanoma. Clin Cancer Res 1;15(19):6158–6166

    Google Scholar 

  171. Lolkema MP, Arkenau HT, Harrington K, Roxburgh P, Morrison R, Roulstone V et al (2011) A phase I study of the combination of intravenous reovirus type 3 Dearing and gemcitabine in patients with advanced cancer. Clin Cancer Res 17:581–588

    Article  CAS  PubMed  Google Scholar 

  172. Kung CP, Raab-Traub N (2008) Epstein-Barr virus latent membrane protein 1 induces expression of the epidermal growth factor receptor through effects on Bcl-3 and STAT3. J Virol 82:5486–5493

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  173. Mita M, Wang Y, Sarantopoulos J et al (2011) A study of REOLYSIN in combination with gemcitabine in patients with advanced pancreatic adenocarcinoma. Mol Targets Cancer Terapeut 10(11):Supplement 1 Poster Board B55

    Google Scholar 

  174. Comins C, Spicer J, Protheroe A, Roulstone V, Twigger K, White CM et al (2010) REO-10: a phase I study of intravenous reovirus and docetaxel in patients with advanced cancer. Clin Cancer Res 16:5564–5572

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  175. Raki M, Kanerva A, Ristimaki A, Desmond RA, Chen DT, Ranki T et al (2005) Combination of gemcitabine and Ad5/3-Delta24, a tropism modified conditionally replicating adenovirus, for the treatment of ovarian cancer. Gene Ther 12:1198–1205

    Article  CAS  PubMed  Google Scholar 

  176. Karapanagiotou EM, Roulstone V, Twigger K, Ball M, Tanay M, Nutting C et al (2012) Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies. Clin Cancer Res 18:2080–2089

    Article  CAS  PubMed  Google Scholar 

  177. Villalona-Calero MA, Lam ET, Otterson GA, et al. (2011) Phase II study of reovirus with paclitaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC) who have Kras or EGFR-activated tumors. In: 14th world lung cancer congress, Abstract MO15.08

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB, Canada

    Chandini Thirukkumaran & Don G. Morris M.D., Ph.D.

  2. Tom Baker Cancer Centre, 1331 29 St. N.W., Calgary, AB, Canada, T2N 4N1

    Chandini Thirukkumaran & Don G. Morris M.D., Ph.D.

  3. Department of Oncology and Medicine, University of Calgary, Calgary, AB, Canada

    Chandini Thirukkumaran & Don G. Morris M.D., Ph.D.

Authors
  1. Chandini Thirukkumaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Don G. Morris M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Don G. Morris M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Wolfgang Walther

  2. Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Berlin, Germany

    Ulrike Stein

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Thirukkumaran, C., Morris, D.G. (2015). Oncolytic Viral Therapy Using Reovirus. In: Walther, W., Stein, U. (eds) Gene Therapy of Solid Cancers. Methods in Molecular Biology, vol 1317. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2727-2_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2727-2_12

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2726-5

  • Online ISBN: 978-1-4939-2727-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation