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Oncolytic viral therapies – the clinical experience

Oncogene volume 24, pages 7802–7816 (2005)Cite this article

Abstract

It has been 9 years since the beginning of the first clinical trial in which an oncolytic virus was administered to cancer patients. Since then, oncolytic viruses from five different species have been taken to phase I and II clinical trials in over 300 cancer patients. While additional studies will be required to ascertain if the efficacy of any of these agents is high enough to warrant adding them to the existing therapeutic regimen, it has been reassuring that DNA viruses engineered to achieve tumor selectivity and RNA viruses with relative inherent natural tumor selectivity have proven reasonably safe at the wide range of doses that were tested. Here, we review the biology and clinical results of these five species of viruses and discuss lessons learned and challenges for the future.

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References

  • Aghi M, Hochberg F and Breakefield XO . (2000). J. Gene Med., 2, 148–164.

  • Assessment of adenoviral vector safety and toxicity: report of the National Institutes of Health Recombinant DNA Advisory Committee (2002) 13, 3–13.

  • Batliwalla FM, Bateman BA, Serrano D, Murray D, Macphail S, Maino VC, Ansel JC, Gregersen PK and Armstrong CA . (1998). Mol. Med., 4, 783–794.

  • Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A and McCormick F . (1996). Science, 274, 373–376.

  • Boviatsis EJ, Park JS, Sena-Esteves M, Kramm CM, Chase M, Efird JT, Wei MX, Breakefield XO and Chiocca EA . (1994a). Cancer Res., 54, 5745–5751.

  • Boviatsis EJ, Scharf JM, Chase M, Harrington K, Kowall NW, Breakefield XO and Chiocca EA . (1994b). Gene Therapy, 1, 323–331.

  • Brown SM, MacLean AR, McKie EA and Harland J . (1997). J. Virol., 71, 9442–9449.

  • Chiocca EA, Abbed KM, Tatter S, Louis DN, Hochberg FH, Barker F, Kracher J, Grossman SA, Fisher JD, Carson K, Rosenblum M, Mikkelsen T, Olson J, Markert J, Rosenfeld S, Nabors LB, Brem S, Phuphanich S, Freeman S, Kaplan R and Zwiebel J . (2004). Mol. Ther., 10, 958–966.

  • Coffey MC, Strong JE, Forsyth PA and Lee PW . (1998). Science, 282, 1332–1334.

  • DeWeese TL, van der Poel H, Li S, Mikhak B, Drew R, Goemann M, Hamper U, DeJong R, Detorie N, Rodriguez R, Haulk T, DeMarzo AM, Piantadosi S, Yu DC, Chen Y, Henderson DR, Carducci MA, Nelson WG and Simons JW . (2001). Cancer Res., 61, 7464–7472.

  • Edelstein M . (2005). Journal of Gene Medicine. World wide web: http://www.wiley.co.uk/genmed/clinical: Wiley Publishers.

    Google Scholar 

  • Enserink M . (2002). Science, 298, 2313.

  • Fong YKN, Jarnagin W, Stanziale S, Guilfoyle B, Gusani N, Joe J, Blumgart L, Lakeman F, Gammon K, Perterkin J, Horsburgh B and Tufaro F . (2002). 38th Annual Meeting of the American Society of Clinical Oncology (ASCO) Orlando, FL.

  • Freeman AI, Gomori JM, Linetsky E, Zakay-Rones Z, Panet A, Libson E, Irving CS, Galun E and Siegal T . (2004). 40th Annual Meeting of the American Society of Clinical Oncology (ASCO) New Orleans, LA.

  • Freytag SO, Khil M, Stricker H, Peabody J, Menon M, DePeralta-Venturina M, Nafziger D, Pegg J, Paielli D, Brown S, Barton K, Lu M, Aguilar-Cordova E and Kim JH . (2002). Cancer Res., 62, 4968–4976.

  • Freytag SO, Stricker H, Pegg J, Paielli D, Pradhan DG, Peabody J, DePeralta-Venturina M, Xia X, Brown S, Lu M and Kim JH . (2003). Cancer Res., 63, 7497–7506.

  • Galanis E, Okuno SH, Nascimento AG, Lewis BD, Lee RA, Oliveira AM, Sloan JA, Atherton P, Edmonson JH, Erlichman C, Randlev B, Wang Q, Freeman S and Rubin J . (2005). Gene Therapy, 12, 437–445.

  • Ganly I, Kirn D, Eckhardt G, Rodriguez GI, Soutar DS, Otto R, Robertson AG, Park O, Gulley ML, Heise C, Von Hoff DD and Kaye SB . (2000). Clin. Cancer Res., 6, 798–806.

  • Gomella LG, Mastrangelo MJ, McCue PA, Maguire HJ, Mulholland SG and Lattime EC . (2001). J. Urol., 166, 1291–1295.

  • Goodrum FD and Ornelles DA . (1998). J. Virol., 72, 9479–9490.

  • Groot-Wassink T, Aboagye EO, Glaser M, Lemoine NR and Vassaux G . (2002). Hum. Gene Ther., 13, 1723–1735.

  • Habib N, Salama H, Abd El Latif Abu Median A, Isac Anis I, Abd Al Aziz RA, Sarraf C, Mitry R, Havlik R, Seth P, Hartwigsen J, Bhushan R, Nicholls J and Jensen S . (2002). Cancer Gene Ther., 9, 254–259.

  • Habib NA, Sarraf CE, Mitry RR, Havlik R, Nicholls J, Kelly M, Vernon CC, Gueret-Wardle D, El-Masry R, Salama H, Ahmed R, Michail N, Edward E and Jensen SL . (2001). Hum. Gene Ther., 12, 219–226.

  • Hamid O, Varterasian ML, Wadler S, Hecht JR, Benson 3rd A, Galanis E, Uprichard M, Omer C, Bycott P, Hackman RC and Shields AF . (2003). J. Clin. Oncol., 21, 1498–1504.

  • Harrow S, Papanastassiou V, Harland J, Mabbs R, Petty R, Fraser M, Hadley D, Patterson J, Brown SM and Rampling R . (2004). Gene Therapy, 11, 1648–1658.

  • Hecht JR, Bedford R, Abbruzzese JL, Lahoti S, Reid TR, Soetikno RM, Kirn DH and Freeman SM . (2003). Clin. Cancer Res., 9, 555–561.

  • Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff DD and Kirn DH . (1997). Nat. Med., 3, 639–645.

  • Heise CC, Williams AM, Xue S, Propst M and Kirn DH . (1999). Cancer Res., 59, 2623–2628.

  • Hermann LL and Coombs KM . (2004). J. Virol., 78, 6171–6179.

  • Hotte SJ, Major PP, Hirte HW, Polawski S, Bamat MK, Rheaume N and Lorence RM . (2003). 39th Annual Meeting of the American Society of Clinical Oncology (ASCO) Chicago, IL.

  • Hu JCMC, Shorrock J, Steiner C, Love R and Coffin C . (2003). 39th Annual Meeting of the American Society of Clinical Oncology (ASCO) Chicago, IL, abstract 742.

  • Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L, Gore M, Ironside J, MacDougall RH, Heise C, Randlev B, Gillenwater AM, Bruso P, Kaye SB, Hong WK and Kirn DH . (2000). Nat. Med., 6, 879–885.

  • Kramm CM, Chase M, Herrlinger U, Jacobs A, Pechan PA, Rainov NG, Sena-Esteves M, Aghi M, Barnett FH, Chiocca EA and Breakefield XO . (1997). Hum. Gene Ther., 8, 2057–2068.

  • Lee SS, Eisenlohr LC, McCue PA, Mastrangelo MJ and Lattime EC . (1994). Cancer Res., 54, 3325–3328.

  • Lorence RM, Rood PA and Kelley KW . (1988). J. Natl. Cancer Inst., 80, 1305–1312.

  • MacKay JA, Deen DF and Szoka Jr FC . (2005). Brain Res., 1035, 139–153.

  • MacKie RM, Stewart B and Brown SM . (2001). Lancet, 357, 525–526.

  • Makower D, Rozenblit A, Kaufman H, Edelman M, Lane ME, Zwiebel J, Haynes H and Wadler S . (2003). Clin. Cancer Res., 9, 693–702.

  • Markert JM, Medlock MD, Rabkin SD, Gillespie GY, Todo T, Hunter WD, Palmer CA, Feigenbaum F, Tornatore C, Tufaro F and Martuza RL . (2000). Gene Therapy, 7, 867–874.

  • Martuza RL, Malick A, Markert JM, Ruffner KL and Coen DM . (1991). Science, 252, 854–856.

  • Mastrangelo MJ, Maguire Jr HC, Eisenlohr LC, Laughlin CE, Monken CE, McCue PA, Kovatich AJ and Lattime EC . (1999). Cancer Gene Ther., 6, 409–422.

  • Mohr I and Gluzman Y . (1996). EMBO J., 15, 4759–4766.

  • Morley S, MacDonald G, Kirn D, Kaye S, Brown R and Soutar D . (2004). Clin. Cancer Res., 10, 4357–4362.

  • Morris DG, Forsyth PA, Paterson AH, Fonseca K, Difrancesco LM, Thompson BG and Coffey MC . (2002). 38th Annual Meeting of the American Society for Clinical Oncology (ASCO) Orlando, FL.

  • Mukherjee S, Haenel T, Himbeck R, Scott B, Ramshaw I, Lake RA, Harnett G, Phillips P, Morey S, Smith D, Davidson JA, Musk AW and Robinson B . (2000). Cancer Gene Ther., 7, 663–670.

  • Mulvihill S, Warren R, Venook A, Adler A, Randlev B, Heise C and Kirn D . (2001). Gene Therapy, 8, 308–315.

  • Nemunaitis J, Cunningham C, Buchanan A, Blackburn A, Edelman G, Maples P, Netto G, Tong A, Randlev B, Olson S and Kirn D . (2001). Gene Therapy, 8, 746–759.

  • Nemunaitis J, Cunningham C, Tong AW, Post L, Netto G, Paulson AS, Rich D, Blackburn A, Sands B, Gibson B, Randlev B and Freeman S . (2003). Cancer Gene Ther., 10, 341–352.

  • Nemunaitis J, Ganly I, Khuri F, Arseneau J, Kuhn J, McCarty T, Landers S, Maples P, Romel L, Randlev B, Reid T, Kaye S and Kirn D . (2000). Cancer Res., 60, 6359–6366.

  • Nemunaitis J, Khuri F, Ganly I, Arseneau J, Posner M, Vokes E, Kuhn J, McCarty T, Landers S, Blackburn A, Romel L, Randlev B, Kaye S and Kirn D . (2001). J. Clin. Oncol., 19, 289–298.

  • O'Shea CC, Johnson L, Bagus B, Choi S, Nicholas C, Shen A, Boyle L, Pandey K, Soria C, Kunich J, Shen Y, Habets G, Ginzinger D and McCormick F . (2004). Cancer Cell, 6, 611–623.

  • Papanastassiou V, Rampling R, Fraser M, Petty R, Hadley D, Nicoll J, Harland J, Mabbs R and Brown M . (2002). Gene Therapy, 9, 398–406.

  • Pecora AL, Rizvi N, Cohen GI, Meropol NJ, Sterman D, Marshall JL, Goldberg S, Gross P, O'Neil JD, Groene WS, Roberts MS, Rabin H, Bamat MK and Lorence RM . (2002). J. Clin. Oncol., 20, 2251–2266.

  • Peng KW, Facteau S, Wegman T, O'Kane D and Russell SJ . (2002). Nat. Med., 8, 527–531.

  • Rampling R, Cruickshank G, Papanastassiou V, Nicoll J, Hadley D, Brennan D, Petty R, MacLean A, Harland J, McKie E, Mabbs R and Brown M . (2000). Gene Therapy, 7, 859–866.

  • Rauen KA, Sudilovsky D, Le JL, Chew KL, Hann B, Weinberg V, Schmitt LD and McCormick F . (2002). Cancer Res., 62, 3812–3818.

  • Reid T, Galanis E, Abbruzzese J, Sze D, Andrews J, Romel L, Hatfield M, Rubin J and Kirn D . (2001). Gene Therapy, 8, 1618–1626.

  • Reid T, Galanis E, Abbruzzese J, Sze D, Wein LM, Andrews J, Randlev B, Heise C, Uprichard M, Hatfield M, Rome L, Rubin J and Kirn D . (2002). Cancer Res., 62, 6070–6079.

  • Rogulski KR, Freytag SO, Zhang K, Gilbert JD, Paielli DL, Kim JH, Heise CC and Kirn DH . (2000). Cancer Res., 60, 1193–1196.

  • Rudin CM, Cohen EE, Papadimitrakopoulou VA, Silverman Jr S, Recant W, El-Naggar AK, Stenson K, Lippman SM, Hong WK and Vokes EE . (2003). J. Clin. Oncol., 21, 4546–4552.

  • Southam CM . (1960). Trans. NY Acad. Sci., 22, 657–673.

  • Todo T, Rabkin SD, Sundaresan P, Wu A, Meehan KR, Herscowitz HB and Martuza RL . (1999). Hum. Gene Ther., 10, 2741–2755.

  • Vasey PA, Shulman LN, Campos S, Davis J, Gore M, Johnston S, Kirn DH, O'Neill V, Siddiqui N, Seiden MV and Kaye SB . (2002). J. Clin. Oncol., 20, 1562–1569.

  • Vogelstein B and Kinzler KW . (2004). Nat. Med., 10, 789–799.

  • Wang Q, Guo J and Jia W . (1997). Gene Therapy, 4, 1300–1304.

  • Wein LM, Wu JT and Kirn DH . (2003). Cancer Res., 63, 1317–1324.

  • Wu JT, Kirn DH and Wein LM . (2004). Bull. Math. Biol., 66, 605–625.

  • Xu RH, Yuan ZY, Guan ZZ, Cao Y, Wang HQ, Hu XH, Feng JF, Zhang Y, Li F, Chen ZT, Wang JJ, Huang JJ, Zhou QH and Song ST . (2003). Ai. Zheng, 22, 1307–1310.

  • Yuan ZY, Zhang L, Li S, Qian XZ and Guan ZZ . (2003). Ai. Zheng, 22, 310–313.

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  1. Department of Neurosurgery, Massachusetts General Hospital, White Building Room 502, 55 Fruit Street, Boston, 02114, MA, USA

    Manish Aghi & Robert L Martuza

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  1. Manish Aghi
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Correspondence to Manish Aghi.

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Aghi, M., Martuza, R. Oncolytic viral therapies – the clinical experience. Oncogene 24, 7802–7816 (2005). https://doi.org/10.1038/sj.onc.1209037

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