Skip to main content
SpringerLink
Log in

Oncolytic Virus Immunotherapy in Sarcoma

  • Chapter
  • First Online:
Immunotherapy of Sarcoma

Abstract

Oncolytic viruses (OVs) are tumor-specific, live agents that actively replicate and function to kill cancer and associated stromal cells through a dual mechanism—a direct, cytotoxic effect and an indirect immune-mediated response. Because OVs are live viral particles, recombinant technologies are used to engineer safe and effective viruses that have a strong anti-tumor response yet maintain low pathogenicity towards normal host cells. Delivery of the virus is accomplished either by the intravenous route or a direct intratumoral injection. Preclinical and clinical investigation of OVs in treatment for sarcomas has increased over the past decade. The first trial investigating use of OVs in resistant sarcoma began in 2010. As such, the use of these viruses in sarcoma is in its infancy. Several trials are currently accruing patients with histologically confirmed soft-tissue and bone sarcoma studying use of oncolytic viruses alone and in combination with chemotherapy, radiation therapy, and immunotherapy. Considering avenues to further enhance the benefit of this modality in the treatment in sarcomas and other tumors offers much promise for the future.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 99.99
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

References

  1. Woolhouse M, Scott F, Hudson Z, Howey R, Chase-Topping M. Human viruses: discovery and emergence. Philos Trans R Soc Lond Ser B Biol Sci. 2012;367(1604):2864–71.

    Article  Google Scholar 

  2. Levaditi C, Nicolau S. Sur la culture de virus vaccinal dans les neoplasmes epitheliaux. CR Soc Biol. 1922;86:928.

    Google Scholar 

  3. Levaditi C, Nicolau S. Affinite du virus herpetique pour les neoplasmes epitheliaux. CR Soc Biol. 1922;87:498–500.

    Google Scholar 

  4. Moore AE. The destructive effect of the virus of Russian Far East encephalitis on the transplantable mouse sarcoma 180. Cancer. 1949;2:525–34.

    Article  CAS  PubMed  Google Scholar 

  5. Moore AE. Effect of inoculation of the viruses of influenza A and herpes simplex on the growth of transplantable tumors in mice. Cancer. 1949;2:516–24.

    Article  CAS  PubMed  Google Scholar 

  6. Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;9:642–62.

    Article  CAS  Google Scholar 

  7. Seliger B. Strategies of tumor immune evasion. BioDrugs. 2005;19:347–54.

    Article  CAS  PubMed  Google Scholar 

  8. Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clin Cancer Res. 2016;22:1865–74.

    Article  CAS  PubMed  Google Scholar 

  9. Heinzerling L, Künzi V, Oberholzer PA, Kündig T, Naim H, Dummer R. Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells. Blood. 2005;106:2287–94.

    Article  CAS  PubMed  Google Scholar 

  10. Zamarin D, Holmgaard RB, Subudhi SK, Park JS, Mansour M, Palese P, Merghoub T, Wolchok JD, Allison JP. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med. 2014;6:226ra32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. https://doi.org/10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  12. Meurs E, Chong K, Galabru J, Thomas NS, Kerr IM, Williams BR, Hovanessian AG. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell. 1990;62:379–90.

    Article  CAS  PubMed  Google Scholar 

  13. Elde NC, Child SJ, Geballe AP, Malik HS. Protein kinase R reveals an evolutionary model for defeating viral mimicry. Nature. 2009;457:485–9.

    Article  CAS  PubMed  Google Scholar 

  14. Clemens MJ. Targets and mechanisms for the regulation of translation in malignant transformation. Oncogene. 2004;23:3180–8.

    Article  CAS  PubMed  Google Scholar 

  15. Yu Z, Chan MK, O-charoenrat P, Eisenberg DP, Shah JP, Singh B, Fong Y, Wong RJ. Enhanced nectin-1 expression and herpes oncolytic sensitivity in highly migratory and invasive carcinoma. Clin Cancer Res. 2005;11:4889–97.

    Article  CAS  PubMed  Google Scholar 

  16. Dorig RE, Marcil A, Chopra A, Richardson CD. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell. 1993;75:295–305.

    Article  CAS  PubMed  Google Scholar 

  17. Anderson BD, Nakamura T, Russell SJ, Peng KW. High CD46 receptor density determines preferential killing of tumor cells by oncolytic measles virus. Cancer Res. 2004;64:4919–26.

    Article  CAS  PubMed  Google Scholar 

  18. Guo P, Huang J, Wang L, Jia D, Yang J, Dillon DA, Zurakowski D, Mao H, Moses MA, Auguste DT. ICAM-1 as a molecular target for triple negative breast cancer. Proc Natl Acad Sci. 2014;111:14710–5.

    Article  CAS  PubMed  Google Scholar 

  19. Au GG, Lincz LF, Enno A, Shafren DR. Oncolytic Coxsackievirus A21 as a novel therapy for multiple myeloma. Br J Haematol. 2007;137:133–41.

    Article  CAS  PubMed  Google Scholar 

  20. Shafren DR, Au GG, Nguyen T, Newcombe NG, Haley ES, Beagley L, Johansson ES, Hersey P, Barry RD. Systemic therapy of malignant human melanoma tumors by a common cold-producing enterovirus, coxsackievirus a21. Clin Cancer Res. 2004;10:53–60.

    Article  CAS  PubMed  Google Scholar 

  21. Shafren DR, Sylvester D, Johansson ES, Campbell IG, Barry RD. Oncolysis of human ovarian cancers by echovirus type 1. Int J Cancer. 2005;115:320–8.

    Article  CAS  PubMed  Google Scholar 

  22. You Z, Fischer DC, Tong X, Hasenburg A, Aguilar-Cordova E, Kieback DG. Coxsackievirus-adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression. Cancer Gene Ther. 2001;8:168–75.

    Article  CAS  PubMed  Google Scholar 

  23. Liapis H, Adler LM, Wick MR, Rader JS. Expression of αv β3 integrin is less frequent in ovarian epithelial tumors of low malignant potential in contrast to ovarian carcinomas. Hum Pathol. 1997;28:443–9.

    Article  CAS  PubMed  Google Scholar 

  24. Morizono K, Xie Y, Ringpis GE, Johnson M, Nassanian H, Lee B, Wu L, Chen IS. Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection. Nat Med. 2005;11:346–52.

    Article  CAS  PubMed  Google Scholar 

  25. Hammond AL, Plemper RK, Zhang J, Schneider U, Russell SJ, Cattaneo R. Single-chain antibody displayed on a recombinant measles virus confers entry through the tumor-associated carcinoembryonic antigen. J Virol. 2001;75:2087–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mansour M, Palese P, Zamarin D. Oncolytic specificity of Newcastle disease virus is mediated by selectivity for apoptosis-resistant cells. J Virol. 2011;85:6015–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bischoff JR, Samuel CE. Mechanism of interferon action. Activation of the human P1/eIF-2α protein kinase by individual reovirus s-class mRNAs: s1 mRNA is a potent activator relative to s4 mRNA. Virology. 1989;172:106–15.

    Article  CAS  PubMed  Google Scholar 

  28. Bischoff JR. An adenovirus mutant that replicates selectively in p-53 deficient human tumor cells. Science. 1996;274:373–6.

    Article  CAS  PubMed  Google Scholar 

  29. He B, Gross M, Roizman B. The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci U S A. 1997;94:843–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ruiz AJ, Russell SJ. MicroRNAs and oncolytic viruses. Curr Opin Virol. 2015;13:40–8.

    Article  CAS  PubMed  Google Scholar 

  31. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011–5.

    Article  CAS  PubMed  Google Scholar 

  32. Liu TC, Hwang T, Park BH, Bell J, Kirn DH. The targeted oncolytic poxvirus JX-594 demonstrates antitumoral, antivascular, and anti-HBV activities in patients with hepatocellular carcinoma. Mol Ther. 2008;14(1):118–28.

    Google Scholar 

  33. Stojdl DF, Abraham N, Knowles S, Marius R, Brasey A, Lichty BD, Brown EG, Sonenberg N, Bell JC. The murine double-stranded RNA-dependent protein kinase pkr is required for resistance to vesicular stomatitis virus. J Virol. 2000;74:9580–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Goldsmith K, Chen W, Johnson DC, Hendricks RL. Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. J Exp Med. 1998;187(3):341–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Thomas MA, Broughton RS, Goodrum FD, Ornelles DA. E4orf1 limits the oncolytic potential of the E1B-55K deletion mutant adenovirus. J Virol. 2009;83:2406–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Duarte S, Carle G, Faneca H, de Lima MC, Pierrefite-Carle V. Suicide gene therapy in cancer: where do we stand now? Cancer Lett. 2012;324(2):160–70.

    Article  CAS  PubMed  Google Scholar 

  37. Fuchita M, Ardiani A, Zhao L, Serve K, Stoddard BL, Black ME. Bacterial cytosine deaminase mutants created by molecular engineering demonstrate improved 5FC-mediated cell killing in vitro and in vivo. Cancer Res. 2009;69(11):4791–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. 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, Kim JH. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res. 2002;62(17):4968–76.

    CAS  PubMed  Google Scholar 

  39. Yamamoto S, Suzuki S, Hoshino A, Akimoto M, Shimada T. Herpes simplex virus thymidine kinase/ganciclovir-mediated killing of tumor cell induces tumor-specific cytotoxic T cells in mice. Cancer Gene Ther. 1997;4(2):91–6.

    PubMed  Google Scholar 

  40. ClinicalTrials.gov. Phase 3 study of ProstAtak® immunotherapy with standard radiation therapy for localized prostate cancer (PrTK03). Clinical Trials Identifier: NCT01436968. (2011). https://clinicaltrials.gov/ct2/show/NCT01436968.

  41. Toda M, Martuza RL, Rabkin SD. Tumor growth inhibition by intratumoral inoculation of defective herpes simplex virus vectors expressing granulocyte macrophage colony-stimulating factor. Mol Ther. 2000;2:324–9.

    Article  CAS  PubMed  Google Scholar 

  42. Willmon CL, Saloura V, Fridlender ZG, Wongthida P, Diaz RM, Thompson J, Kottke T, Federspiel M, Barber G, Albelda SM, Vile RG. Expression of IFN-β enhances both efficacy and safety of oncolytic vesicular stomatitis virus for therapy of mesothelioma. Cancer Res. 2009;69:7713–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. ClinicalTrials.gov. Viral therapy in treating patient with refractory liver cancer or advanced solid tumors. Clinical Trials Identifier: NCT01628640 (2012). https://clinicaltrials.gov/ct2/show/NCT01628640.

  44. ClinicalTrials.gov. Trial of intratumoral administration of recombinant vesicular stomatitis virus in patients with refractory solid tumors. Clinical Trials Identifier: NCT02923466 (2016). https://clinicaltrials.gov/ct2/show/NCT02923466.

  45. Aitken AS, Roy DG, Bourgeois-Daigneault MC. Taking a stab at cancer; oncolytic virus-mediated anti-cancer vaccination strategies. Biomedicine. 2017;5(1):3.

    Google Scholar 

  46. Bilbao R, Bustos M, Alzuguren P, Pajares MJ, Drozdzik M, Qian C, Prieto J. A blood-tumor barrier limits gene transfer to experimental liver cancer: the effect of vasoactive compounds. Gene Ther. 2000;7:1824–32.

    Article  CAS  PubMed  Google Scholar 

  47. Ganesh S, Gonzalez-Edick M, Gibbons D, Van Roey M, Jooss K. Intratumoral coadministration of hyaluronidase enzyme and oncolytic adenoviruses enhances virus potency in metastatic tumor models. Clin Cancer Res. 2008;14:3933–41.

    Article  CAS  PubMed  Google Scholar 

  48. Ebert O, Shinozaki K, Kournioti C, Park MS, García-Sastre A, Woo SL. Syncytia induction enhances the oncolytic potential of vesicular stomatitis virus in virotherapy for cancer. Cancer Res. 2004;64:3265–70.

    Article  CAS  PubMed  Google Scholar 

  49. Tysome JR, Lemoine NR, Wang Y. Combination of anti-angiogenic therapy and virotherapy: arming the oncolytic viruses with anti-angiogenic genes. Curr Opin Mol Ther. 2010;11(6):664–9.

    Google Scholar 

  50. Mahller YY, Vaikunth SS, Ripberger MC, Baird WH, Saeki Y, Cancelas JA, Crombleholme TM, Cripe TP. Tissue inhibitor of metalloproteinase-3 via oncolytic herpesvirus inhibits tumor growth and vascular progenitors. Cancer Res. 2008;68:1170–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 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. Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial. Gene Ther. 2008;15(12):911–20.

    Article  CAS  PubMed  Google Scholar 

  52. Liikanen I, Ahtiainen L, Hirvinen ML, Bramante S, Cerullo V, Nokisalmi P, Hemminki O, Diaconu I, Pesonen S, Koski A, Kangasniemi L, Pesonen SK, Oksanen M, Laasonen L, Partanen K, Joensuu T, Zhao F, Kanerva A, Hemminki A. Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients. Mol Ther. 2013;21:1212–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Cattaneo R, Miest T, Shashkova EV, Barry MA. Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nat Rev Microbiol. 2008;6:529–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Tesfay MZ, Kirk AC, Hadac EM, Griesmann GE, Federspiel MJ, Barber GN, Henry SM, Peng KW, Russell SJ. PEGylation of vesicular stomatitis virus extends virus persistence in blood circulation of passively immunized mice. J Virol. 2013;87:3752–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. O’Riordan CR, Lachapelle A, Delgado C, Parkes V, Wadsworth SC, Smith AE, Francis GE. PEGylation of adenovirus with retention of infectivity and protection from neutralizing antibody in vitro and in vivo. Hum Gene Ther. 1999;10:1349–58.

    Article  PubMed  Google Scholar 

  56. Morrison J, Briggs SS, Green N, Fisher K, Subr V, Ulbrich K, Kehoe S, Seymour LW. Virotherapy of ovarian cancer with polymer-cloaked adenovirus retargeted to the epidermal growth factor receptor. Mol Ther. 2008;16:244–51.

    Article  CAS  PubMed  Google Scholar 

  57. Berger C, Xuereb S, Johnson DC, Watanabe KS, Kiem HP, Greenberg PD, Riddell SR. Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8+ cytotoxic T lymphocytes. J Virol. 2000;74:4465–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Fulci G, Breymann L, Gianni D, Kurozomi K, Rhee SS, Yu J, Kaur B, Louis DN, Weissleder R, Caligiuri MA, Chiocca EA. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc Natl Acad Sci U S A. 2006;103:12873–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Power AT, Wang J, Falls TJ, Paterson JM, Parato KA, Lichty BD, Stojdl DF, Forsyth PA, Atkins H, Bell JC. Carrier cell-based delivery of an oncolytic virus circumvents antiviral immunity. Mol Ther. 2007;15:123–30.

    Article  CAS  PubMed  Google Scholar 

  60. 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. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780–8.

    Article  CAS  PubMed  Google Scholar 

  61. Ganly I, Kirn D, Eckhardt G, et al. A Phase I study of ONYX-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res. 2000;6:798–806.

    CAS  PubMed  Google Scholar 

  62. Lettieri CK, Hingorani P, Kolb EA. Progress of oncolytic viruses in sarcomas. Expert Rev Anticancer Ther. 2012;12(2):229–42.

    Article  CAS  PubMed  Google Scholar 

  63. Dyson N, Harlow E. Adenovirus E1A targets key regulators of cell proliferation. Cancer Surv. 1992;12:161–95.

    CAS  PubMed  Google Scholar 

  64. Lowe SW, Ruley HE. Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Genes Dev. 1993;7(4):535–45.

    Article  CAS  PubMed  Google Scholar 

  65. Nemunaitis J, Ganly I, Khuri F, Arseneau J, Kuhn J, McCarty T, Landers S, Maples P, Romel L, Randlev B, Reid T, Kaye S, Kirn D. Selective replication and oncolysis in p53 mutant tumors with ONYX-015, and E1B55kd gene deleted adenovirus, in patients with advanced head and neck cancer: A Phase II trial. Cancer Res. 2000;60:63596366.

    Google Scholar 

  66. Heise C, Sampson-Johannes A, Williams A, McCormick F, von Hoff DD, Kirn DH. ONYX-015, as E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med. 1997;3:639–45.

    Article  CAS  PubMed  Google Scholar 

  67. Yu W, Fang H. Clinical trials with oncolytic adenovirus in China. Curr Cancer Drug Targets. 2007;7:141–8.

    Article  PubMed  Google Scholar 

  68. ClinicalTrials.gov. Phase I/II study to evaluate the safety and efficacy of telomelysin (OBP-301) in patients with hepatocellular carcinoma. Clinical Trials Identifier: NCT02293850 (2014). https://clinicaltrials.gov/ct2/show/NCT02293850.

  69. ClinicalTrials.gov. Phase I/dose expansion study of enadenotucirev in ovarian cancer patients (OCTAVE). Clinical Trials Identifier: NCT02028117 (2014). https://clinicaltrials.gov/ct2/show/NCT02028117.

  70. Varghese S, Rabkin SD. Oncolytic herpes simplex virus vectors for cancer virotherapy. Cancer Gene Ther. 2002;9:967–78.

    Article  CAS  PubMed  Google Scholar 

  71. Tartaglia J, Pincus S, Paoletti E. Poxvirus-based vectors as vaccine candidates. Crit Rev Immunol. 1990;10:13–30.

    CAS  PubMed  Google Scholar 

  72. Buller RM, Smith GL, Cremer K, Notkins AL, Moss B. Decreased virulence of recombinant vaccinia virus expression in vectors is assoiciated with thymidine kinase-negative phenotype. Nature. 1985;317(6040):813–5.

    Article  CAS  PubMed  Google Scholar 

  73. Abou-Alfa GK, Galle PR, Chao Y, Brown KT, Heo J, Borad MJ, Luca A, Pelusio A, Agathon D, Lusky M, Breitbach C, Burke J, Qin S. PHOCUS: a phase 3 randomized, open-label study comparing the oncolytic immunotherapy Pexa-Vec followed by sorafenib (SOR) vs SOR in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy. J Clin Oncol. 2016;34:15.

    Google Scholar 

  74. ClinicalTrials.gov. Recombinant vaccinia virus administered intravenously in patients with metastatic, refractory colorectal carcinoma. Clinical Trials Identifier: NCT01394939 (2011). https://clinicaltrials.gov/ct2/show/NCT01394939.

  75. ClinicalTrials.gov. Safety study of recombinant vaccinia virus administered intravenously in patients with metastatic, refractory colorectal carcinoma. Clinical Trials Identifier: NCT01380600 (2011). https://clinicaltrials.gov/ct2/show/NCT01380600.

  76. Oncolytics Biotech (ONCY) Announces receipt of FDA orphan drug designation for REOLYSIN. April 2015.

    Google Scholar 

  77. ClinicalTrials.gov. Efficacy study of REOLYSIN® in combination with paclitaxel and carboplatin in platinum-refractory head and neck cancers. Clinical Trials Identifier: NCT01166542 (2010). https://clinicaltrials.gov/ct2/show/NCT01166542.

  78. Ferguson MS, Lemoine NR, Wang Y. Systemic delivery of oncolytic viruses: hopes and hurdles. Adv Virol. 2012;2012:805629.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Seymour LW, Fischer KD. Oncolytic viruses: finally delivering. Br J Cancer. 2016;114(4):357–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Reid T, Galanis E, Abbruzzese J, et al. Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: a phase I trial. Gene Ther. 2001;8(21):1618–26.

    Article  CAS  PubMed  Google Scholar 

  81. Reid T, Warren R, Kirn D. Intravascular adenoviral agents in cancer patients: lessons from clinical trials. Cancer Gene Ther. 2002;9(12):979–86.

    Article  CAS  PubMed  Google Scholar 

  82. Reid TR, Freeman S, Post L, McCormick F, Sze DY. Effects of Onyx-015 among metastatic colorectal cancer patients that have failed prior treatment with 5-FU/leucovorin. Cancer Gene Ther. 2005;12(8):673–81.

    Article  CAS  PubMed  Google Scholar 

  83. Small EJ, Carducci MA, Burke JM, et al. 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. 2006;14(1):107–17.

    Article  CAS  PubMed  Google Scholar 

  84. Ranki T, Pesonen S, Hemminki A, et al. Phase I study with ONCOS-102 for the treatment of solid tumors – an evaluation of clinical response and exploratory analyses of immune markers. J Immunother Cancer. 2016;4:17. https://doi.org/10.1186/s40425-016-0121-5.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Kemeny N, Brown K, Covey A, et al. Phase I, open-label, dose-escalating study of a genetically engineered herpes simplex virus, NV1020, in subjects with metastatic colorectal carcinoma to the liver. Hum Gene Ther. 2006;17(12):1214–24.

    Article  CAS  PubMed  Google Scholar 

  86. Fong Y, Kim T, Bhargava A, et al. A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer. Mol Ther. 2009;17(2):389–94.

    Article  CAS  PubMed  Google Scholar 

  87. Geevarghese SK, Geller DA, De Haan HA, et al. Phase I/II study of oncolytic herpes simplex virus NV1020 in patients with extensively pretreated refractory colorectal cancer metastatic to the liver. Hum Gene Ther. 2010;21(9):1119–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. 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, Lorence RM. I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol. 2002;20:2251–66.

    Google Scholar 

  89. Laurie SA, Bell JC, Atkins HL, et al. A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization. Clin Cancer Res. 2006;12(8):2555–62.

    Article  CAS  PubMed  Google Scholar 

  90. Freeman AI, Zakay-Rones Z, Gomori JM, et al. Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme. Mol Ther. 2006;13(1):221–8.

    Article  CAS  PubMed  Google Scholar 

  91. Hotte SJ, Lorence RM, Hirte HW, et al. An optimized clinical regimen for the oncolytic virus PV701. Clin Cancer Res. 2007;13(3):977–85.

    Article  CAS  PubMed  Google Scholar 

  92. Breitbach CJ, Arulanandam R, De Silva N, et al. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res. 2013;73(4):1265–75. https://doi.org/10.1158/0008-5472.CAN-12-2687.

    Article  CAS  PubMed  Google Scholar 

  93. Clinicaltrials.gov. Safety study of recombinant vaccinia virus to treat refractory solid tumors. ClinicalTrials.gov Identifier: NCT00625456 (2014). https://clinicaltrials.gov/ct2/show/NCT00625456.

  94. Clinicaltrials.gov. Safety study of GL-ONC1, an oncolytic virus, in patients with advanced solid tumors. ClinicalTrials.gov Identifier: NCT00794131 (2015). https://clinicaltrials.gov/ct2/show/NCT00794131.

  95. Clinicaltrials.gov. Safety study of attenuated vaccinia virus (GL-ONC1) with combination therapy in head & neck cancer. ClinicalTrials.gov Identifier: NCT01584284 (2015).

  96. Clinicaltrials.gov. Safety study of modified vaccinia virus to cancer. ClinicalTrials.gov Identifier: NCT00574977 (2015). https://clinicaltrials.gov/ct2/show/NCT00574977.

  97. Vidal L, Pandha HS, Yap TA, et al. A phase I study of intravenous oncolytic reovirus type 3 dearing in patients with advanced cancer. Clin Cancer Res. 2008;14(21):7127–37.

    Article  CAS  PubMed  Google Scholar 

  98. Geletneky K, Huesing J, Rommelaere J, et al. Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol. BMC Cancer. 2012;12:99. https://doi.org/10.1186/1471-2407-12-99.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Clinicaltrials.gov. Parvovirus H-1 (ParvOryx) in patients with metastatic inoperable pancreatic cancer (ParvOryx02). ClinicalTrials.gov Identifier: NCT02653313 (2018). https://clinicaltrials.gov/ct2/show/NCT02653313.

  100. Clinicaltrials.gov. UARK 2014-21 a phase II trial of oncolytic virotherapy by systemic administration of Edmonston strain of measles virus. ClinicalTrials.gov Identifier: NCT02192775 (2017). https://clinicaltrials.gov/ct2/show/NCT02192775.

  101. Clinicaltrials.gov. Vaccine therapy with or without cyclophosphamide in treating patients with recurrent or refractory multiple myeloma. ClinicalTrials.gov Identifier: NCT00450814 (2018). https://clinicaltrials.gov/ct2/show/NCT00450814.

  102. Doronin K, Shashkova EV, May SM, Hofherr SE, Barry MA. Chemical modification with high molecular weight polyethylene glycol reduces transduction of hepatocytes and increases efficacy of intravenously delivered oncolytic adenovirus. Hum Gene Ther. 2009;20:975–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Waddington SN, McVey JH, Bhella D, Parker AL, Barker K, Atoda H, Pink R, Buckley SM, Greig JA, Denby L, Custers J, Morita T, Francischetti IM, Monteiro RQ, Barouch DH, van Rooijen N, Napoli C, Havenga MJ, Nicklin SA, Baker AH. Adenovirus serotype 5 hexon mediates liver gene transfer. Cell. 2008;132:397–409.

    Article  CAS  PubMed  Google Scholar 

  104. Shashkova EV, Doronin K, Senac JS, Barry MA. Macrophage depletion combined with anticoagulant therapy increases therapeutic window of systemic treatment with oncolytic adenovirus. Cancer Res. 2008;68:5896–904.

    Article  CAS  PubMed  Google Scholar 

  105. Eshun FK, Currier MA, Gillespie RA, Fitzpatrick JL, Baird WH, Cripe TP. VEGF blockade decreases tumor uptake of systemic oncolytic herpes virus but enhances therapeutic efficacy when given after virotherapy. Gene Ther. 2010;17(7):922–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Liu TC, Zhang T, Fukuhara H, Kuroda T, Todo T, Canron X, Bikfalvi A, Martuza RL, Kurtz A, Rabkin SD. Dominant-negative fibroblast growth factor receptor expression enhances antitumoral potency of oncolytic herpes simplex virus in neural tumors. Clin Cancer Res. 2006;12(22):6791–9.

    Article  CAS  PubMed  Google Scholar 

  107. Pencavel TD, Wilkinson MJ, Mansfield DC, Khan AA, Seth R, Karapanagiotou EM, Roulstone V, Aguilar RJ, Chen NG, Szalay AA, Hayes AJ, Harrington KJ. Isolated limb perfusion with melphalan, tumour necrosis factor-alpha and oncolytic vaccinia virus improves tumour targeting and prolongs survival in a rat model of advanced extremity sarcoma. Int J Cancer. 2015;136:965–76.

    Article  CAS  PubMed  Google Scholar 

  108. Buijs PR, Verhagen JH, van Eijck CH, van den Hoogen BG. Oncolytic viruses: from bench to bedside with a focus on safety. Hum Vaccin Immunother. 2015;11(7):1573–84.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Andtbacka RH, Amatruda T, Mehnert J, Walker J, Zager JS, Nemunaitis J, Shilkrut M. Interim analysis of phase 2 trial to evaluate biodistribution and shedding of talimogene laherparepvec in unresected stage IIIB-IV melanoma patients. Poster presented at the International Meeting on Replicating Virus Therapeutics, Vancouver, BC, 2016, October.

    Google Scholar 

  110. Clinicaltrials.gov. Single-arm trial to evaluate the biodistribution and shedding of talimogene laherparepvec. Clinical Trials Identifier: NCT02014441 (2013). https://clinicaltrials.gov/ct2/show/results/NCT02014441.

  111. Gangi A, Zager JS. The safety of talimogene laherparepvec for the treatment of advanced melanoma. Expert Opin Drug Saf. 2017;16:265–9.

    CAS  PubMed  Google Scholar 

  112. Hu J, Coffin R, Davis C. A phase I study of oncovexGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res. 2006;12:6737–47.

    Article  CAS  PubMed  Google Scholar 

  113. Harrington KJ, Andtbacka RH, Collichio F, Downey G, Chen L, Szabo Z, Kaufman HL. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial. OncoTargets Ther. 2016;9:7081–93.

    Article  CAS  Google Scholar 

  114. Meager A, Wadhwa M, Bird C, Dilger P, Thorpe R, Newsom-Davis J, Willcox N. Spontaneously occurring neutralizing antibodies against granulocyte–macrophage colony-stimulating factor in patients with autoimmune disease. Immunology. 1999;97(3):526–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Rosen LB, Freeman AF, Yang LM, Jutivorakool K, Olivier KN, Angkasekwinai N, Suputtamongkol Y, Bennett JE, Pyrgos V, Williamson PR, Ding L, Holland SM, Browne SK. Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis. J Immunol. 2013;190(8):3959–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Sakagami T, Uchida K, Suzuki T, Carey BC, Wood RE, Wert SE, Whitsett JA, Trapnell BC, Luisetti M. Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis. N Engl J Med. 2009;361(27):2679–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Downs-Canner S, Guo ZS, Ravindranathan R, Breitbach CJ, O’Malley ME, Jones HL, Moon A, McCart JA, Shuai Y, Zeh HJ, Bartlett DL. Phase 1 study of intravenous oncolytic poxvirus (vvDD) in patients with advanced solid cancers. Mol Ther. 2016;24(8):1492–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Devita VT Jr, Lawrence TS, Rosenberg SA. Cancer principles and practice of oncology. 10th ed. Philadelphia: Wolters Kluwer; 2014. Sarcoma chapter (find page numbers and author of chapter).

    Google Scholar 

  119. Chao J, Chow WA, Somlo G. Novel targeted therapies in the treatment of soft-tissue sarcomas. Expert Rev Anticancer Ther. 2010;10(8):1303–11.

    Article  CAS  PubMed  Google Scholar 

  120. Hingorani P, Kolb E. Past, present, and future of therapies in pediatric sarcomas. Future Oncol. 2010;6(4):605–18.

    Article  CAS  PubMed  Google Scholar 

  121. Bharatan NS, Currier MA, Cripe TP. Differential susceptibility of pediatric sarcoma cells to oncolysis by conditionally replication-competent herpes simplex viruses. J Pediatr Hematol Oncol. 2002;24(6):447–53.

    Article  PubMed  Google Scholar 

  122. Cripe TP, Dunphy EJ, Holub AD, Saini A, Vasi NH, Mahller YY, Collins MH, Snyder JD, Krasnykh V, Curiel DT, Wickham TJ, DeGregori J, Bergelson JM, Currier MA. Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells. Cancer Res. 2001;61:2953–60.

    CAS  PubMed  Google Scholar 

  123. Leddon JL, Chen CY, Currier MA, Wang PY, Jung FA, Denton NL, Cripe KM, Haworth KB, Arnold MA, Gross AC, Eubank TD, Goins WF, Glorioso JC, Cohen JB, Grandi P, Hildeman DA, Cripe TP. Oncolytic HSV virotherapy in murine sarcomas differently triggers an antitumor T-cell response in the absence of viral permissivity. Mol Ther Oncolytics. 2015;1:14010.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Stanziale SF, Petrowsky H, Adusumilli PS, Ben-Porat L, Gonen M, Fong Y. Infection with oncolytic herpes simplex virus-1 induces apoptosis in neighboring human cancer cells: a potential target to increase anticancer activity. Clin Cancer Res. 2004;10:3225–32.

    Article  CAS  PubMed  Google Scholar 

  125. Currier MA, Adams LC, Mahller YY, Cripe TP. Widespread intratumoral virus distribution with fractionated injection enables local control of large human rhabdomyosarcoma xenografts by oncolytic herpes simplex viruses. Cancer Gene Ther. 2005;12:407–16.

    Article  CAS  PubMed  Google Scholar 

  126. Mahller YY, Vaikunth SS, Ripberger MC, Baird WH, Saeki Y, Cancelas JA, Crombleholme TM, Cripe TP. Tissue inhibitor of metalloproteinase-3 via oncolytic herpesvirus inhibits tumor growth and vascular progenitors. Cancer Res. 2008;68(4):1161–8.

    Article  CAS  Google Scholar 

  127. Benencia F, Courreges MC, Conejo-García JR, Buckanovich RJ, Zhang L, Carroll RH, Morgan MA, Coukos G. Oncolytic HSV exerts direct antiangiogenic activity in ovarian carcinoma. Hum Gene Ther. 2005;16:765–78.

    Article  CAS  PubMed  Google Scholar 

  128. Hung J, Anderson R. p53: functions, mutations and sarcomas. Acta Orthop Scand. 1997;273:68–73.

    Article  CAS  Google Scholar 

  129. Seki A, Kodama J, Miyagi Y, Kamimura S, Yoshinouchi M, Kudo T. Amplification of the mdm-2 gene and p53 abnormalities in uterine sarcomas. Int J Cancer. 1997;73:33–7.

    Article  CAS  PubMed  Google Scholar 

  130. Yin L, Liu CX, Nong WX, Chen YZ, Qi Y, Li HA, Hu WH, Sun K, Li F. Mutational analysis of p53 and PTEN in soft tissue sarcoma. Mol Med Rep. 2012;5(2):457–61.

    CAS  PubMed  Google Scholar 

  131. Miller CR, Buchsbaum DJ, Reynolds PN, Douglas JT, Gillespie GY, Mayo MS, Raben D, Curiel DT. Differential susceptibility of primary and established human glioma cells to adenovirus infection: targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer. Cancer Res. 1998;58:5738–48.

    CAS  PubMed  Google Scholar 

  132. Mineta T, Rabkin SD, Yazaki T, Hunter WD, Martuza RL. Attenuated multi–mutated herpes simplex virus–1 for the treatment of malignant gliomas. Nat Med. 1995;1(9):938–43.

    Article  CAS  PubMed  Google Scholar 

  133. Cinatl J Jr, Cinatl J, Michaelis M, Kabickova H, Kotchetkov R, Vogel JU, Doerr HW, Klingebiel T, Driever PH. Potent oncolytic activity of multimutated herpes simplex virus G207 in combination with vincristine against human rhabdomyosarcoma. Cancer Res. 2003;63:1508–14.

    CAS  PubMed  Google Scholar 

  134. Yamamura H, Hashio M, Noguchi M, Sugenoya Y, Osakada M, Hirano N, Sasaki Y, Yoden T, Awata N, Araki N, Tatsuta M, Miyatake SI, Takahashi K. Identification of the transcriptional regulatory sequences of human calponin promoter and their use in targeting a conditionally replicating herpes vector to malignant human soft tissue and bone tumors. Cancer Res. 2001;61:3969–77.

    CAS  PubMed  Google Scholar 

  135. ClinicalTrials.gov. HSV1716 in patients with non-central nervous system (non-CNS) solid tumors. Clinical Trials Identifier: # NCT00931931 (2009). https://clinicaltrials.gov/ct2/show/NCT00931931.

  136. Breitbach CJ, Burke JB, Jonker D. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature. 2011;477(7392):99–102.

    Article  CAS  PubMed  Google Scholar 

  137. ClinicalTrials.gov. Safety study of recombinant vaccinia virus to treat refractory solid tumors in pediatric patients. Clinical Trials Identifier: NCT01169584 (2010). https://clinicaltrials.gov/ct2/show/NCT01169584.

  138. ClinicalTrials.gov. A study of metronomic CP and JX-594 in patients with advanced breast cancer and advanced soft-tissue sarcoma (METROmaJX) (METROmaJX). Clinical Trials Identifier: NCT02630368 (2015). https://clinicaltrials.gov/ct2/show/NCT02630368.

  139. Hingorani P, Zhang W, Lin J, Liu L, Chandan G, Kolb EA. Systemic administration of reovirus (Reolysin) inhibits growth of human sarcoma xenografts. Cancer. 2011;117(8):1764–74.

    Article  CAS  PubMed  Google Scholar 

  140. Mita AC, Sankhala K, Sarantopoulos J, Carmona J, Okuno S, Goel S, Chugh R, Coffey MC, Mettinger K, Mita MM. A phase II study of intravenous (IV) wild-type reovirus (Reolysin) in the treatment of patients with bone and soft tissue sarcomas metastatic to the lung. J Clin Oncol. 2009;27(15S):10524.

    Google Scholar 

  141. Burke MJ, Ahern C, Weigel BJ, Poirier JT, Rudin CM, Chen Y, Cripe TP, Bernhardt MB, Blaney SM. Phase I trial of seneca valley virus (NTX-010) in children with relapsed/refractory solid tumors: a report of the Children’s Oncology Group. Pediatr Blood Cancer. 2015;62(5):743–50.

    Article  CAS  PubMed  Google Scholar 

  142. ClinicalTrials.gov. New castle disease virus (NDV) in glioblastoma multiforme (GBM), sarcoma and neuroblastoma. Clinical Trials Identifier: NCT01174537 (2010). https://clinicaltrials.gov/ct2/show/NCT01174537.

  143. Grimer R, Judson I, Peake D, Seddon B. Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010;2010:506182.

    PubMed  PubMed Central  Google Scholar 

  144. Judson I, Verweij J, Gelderblom H, Hartmann JT, Schoffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT, European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15:415–23.

    Article  CAS  PubMed  Google Scholar 

  145. Meyers DE, Wang AA, Thirukkumaran CM, Morris DG. Current immunotherapeutic strategies to enhance oncolytic virotherapy. Front Oncol. 2017;7:114.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Simpson GR, Relph K, Harrington K, Melcher A, Pandha H. Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances. Oncolytic Virother. 2016;5:1–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Siurala M, Bramante S, Vassilev L, Hirvinen M, Parviainen S, Tähtinen S, Guse K, Cerullo V, Kanerva A, Kipar A, Vähä-Koskela M, Hemminki A. Oncolytic adenovirus and doxorubicin-based chemotherapy results in synergistic antitumor activity against soft-tissue sarcoma. Int J Cancer. 2015;136:945–54.

    Article  CAS  PubMed  Google Scholar 

  148. Gunderson L, Tepper J. Clinical radiation oncology. 4th ed. Philadelphia: Elsevier; 2016. p. 1–19.

    Google Scholar 

  149. Touchefeu Y, Vassaux G, Harrington KJ. Oncolytic viruses in radiation oncology. Radiother Oncol. 2011;99(3):262–70.

    Article  CAS  PubMed  Google Scholar 

  150. Canter RJ, Martinez SR, Tamurian RM, Wilton M, Li CS, Ryu J, Mak W, Monsky WL, Borys D. Radiographic and histologic response to neoadjuvant radiotherapy in patients with soft tissue sarcoma. Ann Surg Oncol. 2010;17(10):2578–84.

    Article  PubMed  PubMed Central  Google Scholar 

  151. Shah D, Borys D, Martinez SR, Li CS, Tamurian RM, Bold RJ, Monjazeb A, Canter RJ. Complete pathologic response to neoadjuvant radiotherapy is predictive of oncological outcome in patients with soft tissue sarcoma. Anticancer Res. 2012;32(9):3911–5.

    PubMed  PubMed Central  Google Scholar 

  152. ClinicalTrials.gov. TVEC and preop radiation for sarcoma. Clinical Trials Identifier: NCT02453191 (2015). https://clinicaltrials.gov/ct2/show/NCT02453191.

  153. ClinicalTrials.gov. Talimogene laherparepvec and radiation therapy in treating patients with newly diagnosed soft tissue sarcoma that can be removed by surgery. Clinical Trials Identfier: NCT02923778 (2016). https://clinicaltrials.gov/ct2/show/NCT02923778.

  154. Liu Z, Ravindranathan R, Kalinski P, Guo ZS, Bartlett DL. Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy. Nat Commun. 2017;8:14754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. ClinicalTrials.gov. Ipilimumab with or without talimogene laherparepvec in unresected melanoma. Clinical Trials Identifier: NCT01740297 (2012). https://clinicaltrials.gov/ct2/show/NCT01740297.

  156. ClinicalTrials.gov. Talimogene laherparepvec and nivolumab in treating patients with refractory lymphomas or advanced or refractory non-melanoma skin cancers. Clinical Trials Identifier: NCT02978625 (2016). https://clinicaltrials.gov/ct2/show/NCT02978625.

  157. ClinicalTrials.gov. Pembrolizumab with or without talimogene laherparepvec or talimogene laherparepvec placebo in unresected melanoma (KEYNOTE-034). Clinical Trials Identifier: NCT02263508 (2014). https://clinicaltrials.gov/ct2/show/NCT02263508.

  158. ClinicalTrials.gov. A Study of talimogene laherparepvec (T-VEC) in combination with pembrolizumab in patients with metastatic and/or locally advanced sarcoma. Clinical Trials Identifier: NCT03069378 (2017). https://clinicaltrials.gov/ct2/show/NCT03069378.

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Oncology, and Bone Marrow Transplantation, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Varun Monga, Seth M. Maliske & Mohammed Milhem

Authors
  1. Varun Monga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seth M. Maliske
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammed Milhem
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammed Milhem .

Editor information

Editors and Affiliations

  1. Department of Sarcoma Medical Oncology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA

    Sandra P. D'Angelo

  2. Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA

    Seth M. Pollack

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Monga, V., Maliske, S.M., Milhem, M. (2019). Oncolytic Virus Immunotherapy in Sarcoma. In: D'Angelo, S., Pollack, S. (eds) Immunotherapy of Sarcoma. Springer, Cham. https://doi.org/10.1007/978-3-319-93530-0_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-93530-0_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-93529-4

  • Online ISBN: 978-3-319-93530-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation