Melanoma pp 699-715 | Cite as

Viral-Based Therapies in Melanoma

  • Ann Silk
  • Praveen K. Bommareddy
  • Howard L. KaufmanEmail author
Reference work entry


Viruses are microscopic organisms that can mediate antitumor activity by commandeering their natural ability to induce innate and adaptive immune responses and through genetic engineering, therapeutic transgene expression by the viral genome. Melanoma is especially well suited for viral-based therapeutics due to the underlying immunogenicity of melanoma cells and the relatively easy ability to inject established tumors in patients. Pharmacologic development of viral therapy in melanoma has focused on viral-based vaccines and oncolytic immunotherapy. In fact, the first approved oncologic application of viral-based agents has been the oncolytic virus, talimogene laherparepvec, for the treatment of advanced melanoma. This chapter will provide the biologic rationale and preclinical proof of concept for viral therapy, describe recent clinical trial results, and discuss some of the unique logistical and biosafety issues associated with the clinical application of viral-based therapeutics. The versatility of viruses as therapeutic agents coupled with a highly tolerable safety profile suggests that viral-based therapies may be important agents for further drug development alone and as part of multicomponent treatment regimens for patients with melanoma.


Immunotherapy Intratumoral treatment Melanoma Oncolytic virus Vaccine 


  1. Adamina M, Rosenthal R, Weber WP, Frey DM, Viehl CT, Bolli M, Huegli RW, Jacob AL, Heberer M, Oertli D, Marti W, Spagnoli GC, Zajac P (2010) Intranodal immunization with a vaccinia virus encoding multiple antigenic epitopes and costimulatory molecules in metastatic melanoma. Mol Ther 18:651–659CrossRefGoogle Scholar
  2. Aitken AS, Roy DG, Martin NT, Sad S, Bell JC, Bourgeois-Daigneault MC (2018) Brief communication; a heterologous oncolytic bacteria-virus prime-boost approach for anticancer vaccination in mice. J Immunother 41:125–129CrossRefGoogle Scholar
  3. Alberts P, Tilgase A, Rasa A, Bandere K, Venskus D (2018) The advent of oncolytic virotherapy in oncology: the Rigvir(R) story. Eur J Pharmacol 837:117–126CrossRefGoogle Scholar
  4. Alkayyal AA, Tai LH, Kennedy MA, de Souza CT, Zhang J, Lefebvre C, Sahi S, Ananth AA, Mahmoud AB, Makrigiannis AP, Cron GO, Macdonald B, Marginean EC, Stojdl DF, Bell JC, Auer RC (2017) NK-cell recruitment is necessary for eradication of peritoneal carcinomatosis with an IL12-expressing maraba virus cellular vaccine. Cancer Immunol Res 5:211–221CrossRefGoogle Scholar
  5. Anderson KV, Bokla L, Nusslein-Volhard C (1985) Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the toll gene product. Cell 42:791–798CrossRefGoogle Scholar
  6. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS (2015) Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 33:2780–2788CrossRefGoogle Scholar
  7. Anthony SJ, Epstein JH, Murray KA, Navarrete-Macias I, Zambrana-Torrelio CM, Solovyov A, Ojeda-Flores R, Arrigo NC, Islam A, Ali Khan S, Hosseini P, Bogich TL, Olival KJ, Sanchez-Leon MD, Karesh WB, Goldstein T, Luby SP, Morse SS, Mazet JA, Daszak P, Lipkin WI (2013) A strategy to estimate unknown viral diversity in mammals. MBio 4:e00598–e00513CrossRefGoogle Scholar
  8. Badrinath N, Jeong YI, Woo HY, Bang SY, Kim C, Heo J, Kang DH, Yoo SY (2018) Local delivery of a cancer-favoring oncolytic vaccinia virus via poly (lactic-co-glycolic acid) nanofiber for theranostic purposes. Int J Pharm 552:437–442CrossRefGoogle Scholar
  9. Bommareddy PK, Patel A, Hossain S, Kaufman HL (2017) Talimogene laherparepvec (T-VEC) and other oncolytic viruses for the treatment of melanoma. Am J Clin Dermatol 18:1–15CrossRefGoogle Scholar
  10. Bommareddy PK, Shettigar M, Kaufman HL (2018) Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol 18:498–513CrossRefGoogle Scholar
  11. Bramante S, Kaufmann JK, Veckman V, Liikanen I, Nettelbeck DM, Hemminki O, Vassilev L, Cerullo V, Oksanen M, Heiskanen R, Joensuu T, Kanerva A, Pesonen S, Matikainen S, Vähä-Koskela M, Koski A, Hemminki A (2015) Treatment of melanoma with a serotype 5/3 chimeric oncolytic adenovirus coding for GM-CSF: results in vitro, in rodents and in humans. Int J Cancer 137:1775–1783CrossRefGoogle Scholar
  12. Cassady KA, Gross M (2002) The herpes simplex virus type 1 U(S)11 protein interacts with protein kinase R in infected cells and requires a 30-amino-acid sequence adjacent to a kinase substrate domain. J Virol 76:2029–2035CrossRefGoogle Scholar
  13. Chesney J, Puzanov I, Collichio F, Singh P, Milhem MM, Glaspy J, Hamid O, Ross M, Friedlander P, Garbe C, Logan TF, Hauschild A, Lebbé C, Chen L, Kim JJ, Gansert J, Andtbacka RHI, Kaufman HL (2018) Randomized, open-label phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with Ipilimumab versus Ipilimumab alone in patients with advanced, unresectable melanoma. J Clin Oncol 36:1658–1667CrossRefGoogle Scholar
  14. Collichio F, Burke L, Proctor A, Wallack D, Collichio A, Long PK, Ollila DW (2018) Implementing a program of talimogene laherparepvec. Ann Surg Oncol 25:1828–1835CrossRefGoogle Scholar
  15. Corrales L, Glickman LH, McWhirter SM, Kanne DB, Sivick KE, Katibah GE, Woo SR, Lemmens E, Banda T, Leong JJ, Metchette K, Dubensky TW Jr, Gajewski TF (2015) Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep 11:1018–1030CrossRefGoogle Scholar
  16. Corrales L, McWhirter SM, Dubensky TW Jr, Gajewski TF (2016) The host STING pathway at the interface of cancer and immunity. J Clin Invest 126:2404–2411CrossRefGoogle Scholar
  17. Corrales L, Matson V, Flood B, Spranger S, Gajewski TF (2017) Innate immune signaling and regulation in cancer immunotherapy. Cell Res 27:96–108CrossRefGoogle Scholar
  18. Curti B, Richards J, Hallmeyer S, Faries M, Andtbacka R, Daniels G, Grose M, Shafren DR (2017) Abstract CT114: the MITCI (phase 1b) study: a novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients with or without previous immune checkpoint therapy treatment. Cancer Res 77:CT114-CTGoogle Scholar
  19. Donina S, Strele I, Proboka G, Auzinš J, Alberts P, Jonsson B, Venskus D, Muceniece A (2015) Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study. Melanoma Res 25:421–426CrossRefGoogle Scholar
  20. Duggan MC, Jochems C, Donahue RN, Richards J, Karpa V, Foust E, Paul B, Brooks T, Tridandapani S, Olencki T, Pan X, Lesinski GB, Schlom J, Carson Iii WE (2016) A phase I study of recombinant (r) vaccinia-CEA(6D)-TRICOM and rFowlpox-CEA(6D)-TRICOM vaccines with GM-CSF and IFN-alpha-2b in patients with CEA-expressing carcinomas. Cancer Immunol Immunother 65:1353–1364CrossRefGoogle Scholar
  21. Eftimie R, Dushoff J, Bridle BW, Bramson JL, Earn DJ (2011) Multi-stability and multi-instability phenomena in a mathematical model of tumor-immune-virus interactions. Bull Math Biol 73:2932–2961CrossRefGoogle Scholar
  22. Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G (2017) Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol 17:97–111CrossRefGoogle Scholar
  23. Galocha B, Hill A, Barnett BC, Dolan A, Raimondi A, Cook RF, Brunner J, McGeoch DJ, Ploegh HL (1997) The active site of ICP47, a herpes simplex virus-encoded inhibitor of the major histocompatibility complex (MHC)-encoded peptide transporter associated with antigen processing (TAP), maps to the NH2-terminal 35 residues. J Exp Med 185:1565–1572CrossRefGoogle Scholar
  24. Gnjatic S, Sawhney NB, Bhardwaj N (2010) Toll-like receptor agonists: are they good adjuvants? Cancer J 16:382–391CrossRefGoogle Scholar
  25. Harrington KJ, Michielin O, Malvehy J, Pezzani Gruter I, Grove L, Frauchiger AL, Dummer R (2017) A practical guide to the handling and administration of talimogene laherparepvec in Europe. Onco Targets Ther 10:3867–3880CrossRefGoogle Scholar
  26. Hiraoka K, Inagaki A, Kato Y, Huang TT, Mitchell LA, Kamijima S, Takahashi M, Matsumoto H, Hacke K, Kruse CA, Ostertag D, Robbins JM, Gruber HE, Jolly DJ, Kasahara N (2017) Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anticancer immunity. Neuro-Oncology 19:918–929CrossRefGoogle Scholar
  27. Kaufman H, Schlom J, Kantor J (1991) A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA). Int J Cancer 48:900–907CrossRefGoogle Scholar
  28. Kaufman HL, Flanagan K, Lee CS, Perretta DJ, Horig H (2002) Insertion of interleukin-2 (IL-2) and interleukin-12 (IL-12) genes into vaccinia virus results in effective anti-tumor responses without toxicity. Vaccine 20:1862–1869CrossRefGoogle Scholar
  29. Kaufman HL, DeRaffele G, Mitcham J, Moroziewicz D, Cohen SM, Hurst-Wicker KS, Cheung K, Lee DS, Divito J, Voulo M, Donovan J, Dolan K, Manson K, Panicali D, Wang E, Hörig H, Marincola FM (2005) Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. J Clin Investig 115:1903–1912CrossRefGoogle Scholar
  30. Kaufman HL, Cohen S, Cheung K, DeRaffele G, Mitcham J, Moroziewicz D, Schlom J, Hesdorffer C (2006) Local delivery of vaccinia virus expressing multiple costimulatory molecules for the treatment of established tumors. Hum Gene Ther 17:239–244CrossRefGoogle Scholar
  31. Kaufman HL, Kohlhapp FJ, Zloza A (2015) Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov 14:642–662CrossRefGoogle Scholar
  32. Kaufman HL, Amatruda T, Reid T, Gonzalez R, Glaspy J, Whitman E, Harrington K, Nemunaitis J, Zloza A, Wolf M, Senzer NN (2016) Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study. J Immunother Cancer 4:12CrossRefGoogle Scholar
  33. Komorowski MP, McGray AR, Kolakowska A, Eng K, Gil M, Opyrchal M, Litwinska B, Nemeth MJ, Odunsi KO, Kozbor D (2016) Reprogramming antitumor immunity against chemoresistant ovarian cancer by a CXCR4 antagonist-armed viral oncotherapy. Mol Ther Oncol 3:16034CrossRefGoogle Scholar
  34. Larson C, Oronsky B, Varner G, Caroen S, Burbano E, Insel E, Hedjran F, Carter CA, Reid TR (2018) A practical guide to the handling and administration of personalized transcriptionally attenuated oncolytic adenoviruses (PTAVs). Oncoimmunology 7:e1478648CrossRefGoogle Scholar
  35. Lewis FM, Chernak E, Goldman E, Li Y, Karem K, Damon IK, Henkel R, Newbern EC, Ross P, Johnson CC (2006) Ocular vaccinia infection in laboratory worker, Philadelphia, 2004. Emerg Infect Dis 12:134–137CrossRefGoogle Scholar
  36. Lin L, Wei J, Chen Y, Huang A, Li KK-W, Zhang W (2014) Induction of antigen-specific immune responses by dendritic cells transduced with a recombinant lentiviral vector encoding MAGE-A3 gene. J Cancer Res Clin Oncol 140:281–289CrossRefGoogle Scholar
  37. Linette GP, Hamid O, Whitman ED, Nemunaitis JJ, Chesney J, Agarwala SS, Starodub A, Barrett JA, Marsh A, Martell LA, Cho A, Reed TD, Youssoufian H, Vergara-Silva A (2013) A phase I open-label study of ad-RTS-hIL-12, an adenoviral vector engineered to express hIL-12 under the control of an oral activator ligand, in subjects with unresectable stage III/IV melanoma. J Clin Oncol 31:3022Google Scholar
  38. Mahasa KJ, Eladdadi A, de Pillis L, Ouifki R (2017) Oncolytic potency and reduced virus tumor-specificity in oncolytic virotherapy. A mathematical modelling approach. PLoS One 12:e0184347CrossRefGoogle Scholar
  39. Marabelle A, Andtbacka R, Harrington K, Melero I, Leidner R, de Baere T, Robert C, Ascierto PA, Baurain JF, Imperiale M, Rahimian S, Tersago D, Klumper E, Hendriks M, Kumar R, Stern M, Ohrling K, Massacesi C, Tchakov I, Tse A, Douillard JY, Tabernero J, Haanen J, Brody J (2018) Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT). Ann Oncol 29:2163CrossRefGoogle Scholar
  40. McAneny D, Ryan CA, Beazley RM, Kaufman HL (1996) Results of a phase I trial of a recombinant vaccinia virus that expresses carcinoembryonic antigen in patients with advanced colorectal cancer. Ann Surg Oncol 3:495–500CrossRefGoogle Scholar
  41. Nishio N, Diaconu I, Liu H, Cerullo V, Caruana I, Hoyos V, Bouchier-Hayes L, Savoldo B, Dotti G (2014) Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors. Cancer Res 74:5195–5205CrossRefGoogle Scholar
  42. Ottolino-Perry K, Diallo JS, Lichty BD, Bell JC, McCart JA (2010) Intelligent design: combination therapy with oncolytic viruses. Mol Ther 18:251–263CrossRefGoogle Scholar
  43. Pandha H, Harrington K, Ralph C, Melcher A, Gupta S, Akerley W, Sandborn RE, Rudin C, Rosenberg J, Kaufman D, Schmidt E, Grose M, Shafren DR (2017a) Abstract CT115: phase 1b KEYNOTE 200 (STORM study): a study of an intravenously delivered oncolytic virus, Coxsackievirus A21 in combination with pembrolizumab in advanced cancer patients. Cancer Res 77:CT115-CTCrossRefGoogle Scholar
  44. Pandha HS, Ralph C, Harrington K, Curti BD, Sanborn RE, Akerley WL, Gupta S, Rudin CM, Rosenberg JE, Kaufman DR, Schmidt EV, Grose M, Shafren D (2017b) Keynote-200 phase 1b: a novel combination study of intravenously delivered coxsackievirus A21 and pembrolizumab in advanced cancer patients. J Clin Oncol 35:TPS3108-TPSCrossRefGoogle Scholar
  45. Pelka P, Miller MS, Cecchini M, Yousef AF, Bowdish DM, Dick F, Whyte P, Mymryk JS (2011) Adenovirus E1A directly targets the E2F/DP-1 complex. J Virol 85:8841–8851CrossRefGoogle Scholar
  46. Pelner L, Fowler GA, Nauts HC (1958) Effects of concurrent infections and their toxins on the course of leukemia. Acta Medica Scand Suppl 338:1–47Google Scholar
  47. Perez OD, Logg CR, Hiraoka K, Diago O, Burnett R, Inagaki A, Jolson D, Amundson K, Buckley T, Lohse D, Lin A, Burrascano C, Ibanez C, Kasahara N, Gruber HE, Jolly DJ (2012) Design and selection of Toca 511 for clinical use: modified retroviral replicating vector with improved stability and gene expression. Mol Ther 20:1689–1698CrossRefGoogle Scholar
  48. Pol JG, Zhang L, Bridle BW, Stephenson KB, Resseguier J, Hanson S, Chen L, Kazdhan N, Bramson JL, Stojdl DF, Wan Y, Lichty BD (2014) Maraba virus as a potent oncolytic vaccine vector. Mol Ther 22:420–429CrossRefGoogle Scholar
  49. Pol JG, SAA BY, Tang N, Stephenson KB, Atherton MJ, Hanwell D, El-Warrak A, Goldstein A, Moloo B, Turner PV, Lopez R, LaFrance S, Evelegh C, Denisova G, Parsons R, Millar J, Stoll G, Martin CG, Pomoransky J, Breitbach CJ, Bramson JL, Bell JC, Wan Y, Stojdl DF, Lichty BD, McCart JA (2018) Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials. OncoImmunology 19:8(1):e1512329.CrossRefGoogle Scholar
  50. Riaz N, Havel JJ, Makarov V, Desrichard A, Urba WJ, Sims JS, Hodi FS, Martin-Algarra S, Mandal R, Sharfman WH, Bhatia S, Hwu WJ, Gajewski TF, Slingluff CL Jr, Chowell D, Kendall SM, Chang H, Shah R, Kuo F, Morris LGT, Sidhom JW, Schneck JP, Horak CE, Weinhold N, Chan TA (2017) Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell 171:934–49.e16CrossRefGoogle Scholar
  51. Ribas A, Dummer R, Puzanov I, Vander Walde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV (2017a) Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell 170:1109–19.e10CrossRefGoogle Scholar
  52. Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV (2017b) Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell 170:1109–19.e10CrossRefGoogle Scholar
  53. Roulstone V, Pedersen M, Kyula J, Mansfield D, Khan AA, McEntee G, Wilkinson M, Karapanagiotou E, Coffey M, Marais R, Jebar A, Errington-Mais F, Melcher A, Vile R, Pandha H, McLaughlin M, Harrington KJ (2015) BRAF- and MEK-targeted small molecule inhibitors exert enhanced antimelanoma effects in combination with oncolytic reovirus through ER stress. Mol Ther 23:931–942CrossRefGoogle Scholar
  54. Sagiv-Barfi I, Czerwinski DK, Levy S, Alam IS, Mayer AT, Gambhir SS, Levy R (2018) Eradication of spontaneous malignancy by local immunotherapy. Sci Transl Med 10. Scholar
  55. Salaun B, Lebecque S, Matikainen S, Rimoldi D, Romero P (2007) Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin Cancer Res 13:4565–4574CrossRefGoogle Scholar
  56. Savontaus MJ, Sauter BV, Huang TG, Woo SL (2002) Transcriptional targeting of conditionally replicating adenovirus to dividing endothelial cells. Gene Ther 9:972–979CrossRefGoogle Scholar
  57. Schumacher TN, Schreiber RD (2015) Neoantigens in cancer immunotherapy. Science 348:69–74CrossRefGoogle Scholar
  58. 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 27:5763–5771CrossRefGoogle Scholar
  59. Sick E, Jeanne A, Schneider C, Dedieu S, Takeda K, Martiny L (2012) CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest. Br J Pharmacol 167:1415–1430CrossRefGoogle Scholar
  60. Silk AW, Kaufman H, Gabrail N, Mehnert J, Bryan J, Norrell J, Medina D, Bommareddy P, Shafren D, Grose M, Zloza A (2017) Abstract CT026: phase 1b study of intratumoral Coxsackievirus A21 (CVA21) and systemic pembrolizumab in advanced melanoma patients: interim results of the CAPRA clinical trial. Cancer Res 77:CT026-CTGoogle Scholar
  61. Symons JA, Alcami A, Smith GL (1995) Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity. Cell 81:551–560CrossRefGoogle Scholar
  62. Takahashi M, Valdes G, Hiraoka K, Inagaki A, Kamijima S, Micewicz E, Gruber HE, Robbins JM, Jolly DJ, McBride WH, Iwamoto KS, Kasahara N (2014) Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector. Cancer Gene Ther 21:405–410CrossRefGoogle Scholar
  63. Toda M, Rabkin SD, Kojima H, Martuza RL (1999) Herpes simplex virus as an in situ cancer vaccine for the induction of specific anti-tumor immunity. Hum Gene Ther 10:385–393CrossRefGoogle Scholar
  64. Tuve S, Wang H, Ware C, Liu Y, Gaggar A, Bernt K, Shayakhmetov D, Li Z, Strauss R, Stone D, Lieber A (2006) A new group B adenovirus receptor is expressed at high levels on human stem and tumor cells. J Virol 80:12109–12120CrossRefGoogle Scholar
  65. Twitty CG, Diago OR, Hogan DJ, Burrascano C, Ibanez CE, Jolly DJ, Ostertag D (2016) Retroviral replicating vectors deliver cytosine deaminase leading to targeted 5-fluorouracil-mediated cytotoxicity in multiple human cancer types. Hum Gene Ther Methods 27:17–31CrossRefGoogle Scholar
  66. Wittek R (2006) Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy. Int J Infect Dis 10:193–201CrossRefGoogle Scholar
  67. Zafar S, Parviainen S, Siurala M, Hemminki O, Havunen R, Tahtinen S, Bramante S, Vassilev L, Wang H, Lieber A, Hemmi S, de Gruijl T, Kanerva A, Hemminki A (2017) Intravenously usable fully serotype 3 oncolytic adenovirus coding for CD40L as an enabler of dendritic cell therapy. Oncoimmunology 6:e1265717CrossRefGoogle Scholar
  68. Zajac P, Oertli D, Marti W, Adamina M, Bolli M, Guller U, Noppen C, Padovan E, Schultz-Thater E, Heberer M, Spagnoli G (2003) Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients. Hum Gene Ther 14:1497–1510CrossRefGoogle Scholar
  69. Zhang J, Tai LH, Ilkow CS, Alkayyal AA, Ananth AA, de Souza CT, Wang J, Sahi S, Ly L, Lefebvre C, Falls TJ, Stephenson KB, Mahmoud AB, Makrigiannis AP, Lichty BD, Bell JC, Stojdl DF, Auer RC (2014) Maraba MG1 virus enhances natural killer cell function via conventional dendritic cells to reduce postoperative metastatic disease. Mol Ther 22:1320–1332CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ann Silk
    • 1
  • Praveen K. Bommareddy
    • 1
    • 2
  • Howard L. Kaufman
    • 3
    • 4
    Email author
  1. 1.Rutgers Cancer institute of New JerseyNew BrunswickUSA
  2. 2.School of Graduate StudiesRutgers UniversityNew BrunswickUSA
  3. 3.Division of Surgical OncologyMassachusetts General HospitalBostonUSA
  4. 4.Replimune, Inc.WoburnUSA

Section editors and affiliations

  • Keith T. Flaherty
    • 1
  • Boris C. Bastian
    • 2
  • Hensin Tsao
    • 3
    • 4
  • F. Stephen Hodi
    • 5
    • 6
  1. 1.Henri and Belinda Termeer Center for Targeted TherapiesMGH Cancer CenterCambridgeUSA
  2. 2.Departments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer CenterUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.AuburndaleUSA
  4. 4.Harvard-MIT Health Sciences and TechnologyCambridgeUSA
  5. 5.FraminghamUSA
  6. 6.Department of Medicine, Brigham and Women's HospitalDana-Farber Cancer InstituteBostonUSA

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