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Viruses in cancer treatment


Soon after the discovery that viruses cause human disease, started the idea of using viruses to treat cancer. After the initial indiscriminate use, crude preparations of each novel virus in the early twentieth century, a second wave of virotherapy blossomed in the 60s with purified and selected viruses. Responses were rare and short-lived. Immune rejection of the oncolytic viruses was identified as the major problem and virotherapy was abandoned. During the past two decades virotherapy has re-emerged with engineered viruses, with a trend towards using them as tumor-debulking immunostimulatory agents combined with radio or chemotherapy. Currently, oncolytic Reovirus, Herpes, and Vaccinia virus are in late phase clinical trials. Despite the renewed hope, efficacy will require improving systemic tumor targeting, overcoming stroma barriers for virus spread, and selectively stimulating immune responses against tumor antigens but not against the virus. Virotherapy history, viruses, considerations for clinical trials, and hurdles are briefly overviewed.

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  1. 1.

    Javier RT, Butel JS (2008) The history of tumor virology. Cancer Res 68:7693–7706

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Sinkovics J, Horvath J, Szabo-Szabari M (1994) Human cancer vaccines. Leukemia 8(Suppl 1):S194–S197

    PubMed  Google Scholar 

  3. 3.

    Kelly E, Russell SJ (2007) History of oncolytic viruses: genesis to genetic engineering. Mol Ther 15:651–659

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    De Pace N (1912) Sulla scomparsa di un enorme cranco vegetante del collo dell′utero senza cura chirurgica. Ginecologia 9:82–89

    Google Scholar 

  5. 5.

    Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM (1991) Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 252:854–856

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Alemany R, Cascallo M (2009) Oncolytic adenoviruses from the perspective of the immune system. Future Microbiol 4:527–536

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Karapanagiotou EM, Roulstone V, Twigger K, Ball M, Tanay M, Nutting C, Newbold K, Gore ME, Larkin J, Syrigos KN, Coffey M, Thompson B, Mettinger K, Vile RG, Pandha HS, Hall GD, Melcher AA, Chester J, Harrington KJ (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

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Yaacov B, Lazar I, Tayeb S, Frank S, Izhar U, Lotem M, Perlman R, Ben-Yehuda D, Zakay-Rones Z, Panet A (2012) Extracellular matrix constituents interfere with Newcastle disease virus spread in solid tissue and diminish its potential oncolytic activity. J Gen Virol 93:1664–1672

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Hotte SJ, Lorence RM, Hirte HW, Polawski SR, Bamat MK, O’Neil JD, Roberts MS, Groene WS, Major PP (2007) An optimized clinical regimen for the oncolytic virus PV701. Clin Cancer Res 13:977–985

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Lam HY, Yeap SK, Rasoli M, Omar AR, Yusoff K, Suraini AA, Alitheen NB (2011) Safety and clinical usage of newcastle disease virus in cancer therapy. J Biomed Biotechnol 2011:718710

    PubMed  Article  Google Scholar 

  11. 11.

    Galanis E (2010) Therapeutic potential of oncolytic measles virus: promises and challenges. Clin Pharmacol Ther 88:620–625

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Galanis E, Hartmann LC, Cliby WA, Long HJ, Peethambaram PP, Barrette BA, Kaur JS, Haluska PJ Jr, Aderca I, Zollman PJ, Sloan JA, Keeney G, Atherton PJ, Podratz KC, Dowdy SC, Stanhope CR, Wilson TO, Federspiel MJ, Peng KW, Russell SJ (2010) Phase I trial of intraperitoneal administration of an oncolytic measles virus strain engineered to express carcinoembryonic antigen for recurrent ovarian cancer. Cancer Res 70:875–882

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Senzer NN, Kaufman HL, Amatruda T, Nemunaitis M, Reid T, Daniels G, Gonzalez R, Glaspy J, Whitman E, Harrington K, Goldsweig H, Marshall T, Love C, Coffin R, Nemunaitis JJ (2009) Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol 27:5763–5771

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, Nieva J, Hwang TH, Moon A, Patt R, Pelusio A, Le Boeuf F, Burns J, Evgin L, De Silva N, Cvancic S, Robertson T, Je JE, Lee YS, Parato K, Diallo JS, Fenster A, Daneshmand M, Bell JC, Kirn DH (2011) Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 477:99–102

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Smith RR, Huebner RJ, Rowe WP, Schatten WF, Thomas LB (1956) Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 9:1211–1218

    PubMed  Article  Google Scholar 

  16. 16.

    Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A, McCormick F (1996) An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274:373–376

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Fueyo J, Gomez-Manzano C, Alemany R, Lee PS, McDonnell TJ, Mitlianga P, Shi YX, Levin VA, Yung WK, Kyritsis AP (2000) A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 19:2–12

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Heise C, Hermiston T, Johnson L, Brooks G, Sampson-Johannes A, Williams A, Hawkins L, Kirn D (2000) An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med 6:1134–1139

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Small EJ, Carducci MA, Burke JM, Rodriguez R, Fong L, van Ummersen L, Yu DC, Aimi J, Ando D, Working P, Kirn D, Wilding G (2006) A phase I trial of intravenous CG7870, a replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic prostate cancer. Mol Ther 14:107–117

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Pesonen S, Kangasniemi L, Hemminki A (2011) Oncolytic adenoviruses for the treatment of human cancer: focus on translational and clinical data. Mol Pharm 8:12–28

    PubMed  Article  CAS  Google Scholar 

  21. 21.

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

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Ribas A, Chmielowski B, Glaspy JA (2009) Do we need a different set of response assessment criteria for tumor immunotherapy? Clin Cancer Res 15:7116–7118

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Ottolino-Perry K, Diallo JS, Lichty BD, Bell JC, McCart JA (2010) Intelligent design: combination therapy with oncolytic viruses. Mol Ther 18:251–263

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63:136–151

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Coughlan L, Alba R, Parker AL, Bradshaw AC, McNeish IA, Nicklin SA, Baker AH (2011) Tropism-modification strategies for targeted gene delivery using adenoviral vectors. Viruses 2:2290–2355

    Article  Google Scholar 

  26. 26.

    Choi JW, Lee JS, Kim SW, Yun CO (2012) Evolution of oncolytic adenovirus for cancer treatment. Adv Drug Deliv Rev 64:720–729

    Google Scholar 

  27. 27.

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

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Akram A, Inman RD (2012) Immunodominance: a pivotal principle in host response to viral infections. Clin Immunol 143:99–115

    PubMed  Article  CAS  Google Scholar 

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Thanks to Cristina Balagué for critical reading. Dedicated to the memory of Dr. Alexander Pereboev.

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Correspondence to R. Alemany.

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Alemany, R. Viruses in cancer treatment. Clin Transl Oncol 15, 182–188 (2013).

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  • Virotherapy
  • Oncolytic
  • Virus
  • Immunotherapy