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Scientifica
Volume 2014 (2014), Article ID 862925, 7 pages
http://dx.doi.org/10.1155/2014/862925
Review Article

Oncolytic Immunotherapy: Where Are We Clinically?

1Cancer Gene Therapy Group, Haartman Institute, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland
2TILT Biotherapeutics Ltd., P. Hesperiankatu 37A22, 00260 Helsinki, Finland

Received 6 November 2013; Accepted 16 December 2013; Published 16 January 2014

Academic Editors: H. J. Haisma and H. Hofler

Copyright © 2014 Akseli Hemminki. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Westphal, S. Yla-Herttuala, J. Martin, et al., “Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial,” The Lancet Oncology, vol. 14, no. 9, pp. 823–833, 2013. View at Publisher · View at Google Scholar
  2. J. J. Pan, S. W. Zhang, C. B. Chen et al., “Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term prognosis of advanced nasopharyngeal carcinoma,” Journal of Clinical Oncology, vol. 27, no. 5, pp. 799–804, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. V. Cerullo, A. Koski, M. Vaha-Koskela, and A. Hemminki, “Chapter eight—oncolytic adenoviruses for cancer immunotherapy: data from mice, hamsters, and humans,” Advances in Cancer Research, vol. 115, pp. 265–318, 2012.
  4. L. Kangasniemi and A. Hemminki, “Oncolytic adenovirus research and applications,” Future Virology, vol. 5, no. 6, pp. 745–761, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Raki, D. T. Rein, A. Kanerva, and A. Hemminki, “Gene transfer approaches for gynecological diseases,” Molecular Therapy, vol. 14, no. 2, pp. 154–163, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Bramante, A. Koski, A. Kipar, et al., “Serotype chimeric oncolytic adenovirus coding for GM-CSF for treatment of sarcoma in rodents and humans,” International Journal of Cancer, 2013.
  7. J. D. Dias, I. Liikanen, K. Guse et al., “Targeted chemotherapy for head and neck cancer with a chimeric oncolytic adenovirus coding for bifunctional suicide protein FCU1,” Clinical Cancer Research, vol. 16, no. 9, pp. 2540–2549, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Raki, T. Hakkarainen, G. J. Bauerschmitz et al., “Utility of TK/GCV in the context of highly effective oncolysis mediated by a serotype 3 receptor targeted oncolytic adenovirus,” Gene Therapy, vol. 14, no. 19, pp. 1380–1388, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Rajecki, A. Kangasmäki, L. Laasonen et al., “Sodium iodide symporter SPECT imaging of a patient treated with oncolytic adenovirus Ad5/3-Δ24-hNIS,” Molecular Therapy, vol. 19, no. 4, pp. 629–631, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. E. Kelly and S. J. Russell, “History of oncolytic viruses: genesis to genetic engineering,” Molecular Therapy, vol. 15, no. 4, pp. 651–659, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. J. R. Bischoff, D. H. Kirn, A. Williams et al., “An adenovirus mutant that replicates selectively in p53-deficient human tumor cells,” Science, vol. 274, no. 5286, pp. 373–376, 1996. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Mineta, S. D. Rabkin, and R. L. Martuza, “Treatment of malignant gliomas using ganciclovir-hypersensitive, ribonucleotide reductase-deficient herpes simplex viral mutant,” Cancer Research, vol. 54, no. 15, pp. 3963–3966, 1994. View at Scopus
  13. M. J. Mastrangelo, H. C. Maguire Jr., L. C. Eisenlohr et al., “Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma,” Cancer Gene Therapy, vol. 6, no. 5, pp. 409–422, 1999. View at Scopus
  14. T. R. Reid, S. Freeman, L. Post, F. McCormick, and D. Y. Sze, “Effects of Onyx-015 among metastatic colorectal cancer patients that have failed prior treatment with 5-FU/leucovorin,” Cancer Gene Therapy, vol. 12, no. 8, pp. 673–681, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. A. K. Koski, H. Ahtinen, H. Liljenback, et al., “FDG-PET and CT in response evaluation of oncolytic adenovirus treatments of patients with advanced cancer,” Human Gene Therapy, vol. 24, no. 12, pp. 1029–1041, 2013. View at Publisher · View at Google Scholar
  16. J. D. Wolchok, A. Hoos, S. O'Day et al., “Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria,” Clinical Cancer Research, vol. 15, no. 23, pp. 7412–7420, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. V. Cerullo, S. Pesonen, I. Diaconu et al., “Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients,” Cancer Research, vol. 70, no. 11, pp. 4297–4309, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Hemminki, “Portrait of a leader in immunotherapeutics: oncolytic viruses for treatment of cancer,” Human Vaccines & Immunotherapeutics, vol. 8, no. 8, pp. 1018–1021, 2012.
  19. A. Koski, L. Kangasniemi, S. Escutenaire et al., “Treatment of cancer patients with a serotype 5/3 chimeric oncolytic adenovirus expressing GMCSF,” Molecular Therapy, vol. 18, no. 10, pp. 1874–1884, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Pesonen, I. Diaconu, V. Cerullo et al., “Integrin targeted oncolytic adenoviruses Ad5-D24-RGD and Ad5-RGD-D24-GMCSF for treatment of patients with advanced chemotherapy refractory solid tumors,” International Journal of Cancer, vol. 130, no. 8, pp. 1937–1947, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. O. Hemminki, I. Diaconu, V. Cerullo, et al., “Ad3-hTERT-E1A, a fully serotype 3 oncolytic adenovirus, in patients with chemotherapy refractory cancer,” Molecular Therapy, vol. 20, no. 9, pp. 1821–1830, 2012. View at Publisher · View at Google Scholar
  22. S. Pesonen, I. Diaconu, L. Kangasniemi et al., “Oncolytic immunotherapy of advanced solid tumors with a CD40L-expressing replicating adenovirus: assessment of safety and immunologic responses in patients,” Cancer Research, vol. 72, no. 7, pp. 1621–1631, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. P. Nokisalmi, S. Pesonen, S. Escutenaire et al., “Oncolytic adenovirus ICOVIR-7 in patients with advanced and refractory solid tumors,” Clinical Cancer Research, vol. 16, no. 11, pp. 3035–3043, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. A. Kanerva, P. Nokisalmi, I. Diaconu, et al., “Antiviral and antitumor T-cell immunity in patients treated with GM-CSF-coding oncolytic adenovirus,” Clinical Cancer Research, vol. 19, no. 10, pp. 2734–2744, 2013. View at Publisher · View at Google Scholar
  25. I. Liikanen, L. Ahtiainen, M. L. Hirvinen, et al., “Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients,” Molecular Therapy, vol. 21, no. 6, pp. 1212–1223, 2013. View at Publisher · View at Google Scholar
  26. R. J. Prestwich, F. Errington, R. M. Diaz et al., “The case of oncolytic viruses versus the immune system: waiting on the judgment of Solomon,” Human Gene Therapy, vol. 20, no. 10, pp. 1119–1132, 2009. View at Scopus
  27. K. A. Parato, B. D. Lichty, and J. C. Bell, “Diplomatic immunity: turning a foe into an ally,” Current Opinion in Molecular Therapeutics, vol. 11, no. 1, pp. 13–21, 2009. View at Scopus
  28. V. Cerullo, I. Diaconu, V. Romano, et al., “An oncolytic adenovirus enhanced for toll-like receptor 9 stimulation increases antitumor immune responses and tumor clearance,” Molecular Therapy, vol. 20, no. 11, pp. 2076–2086, 2012. View at Publisher · View at Google Scholar
  29. I. Diaconu, V. Cerullo, S. Escutenaire et al., “Human adenovirus replication in immunocompetent Syrian hamsters can be attenuated with chlorpromazine or cidofovir,” Journal of Gene Medicine, vol. 12, no. 5, pp. 435–445, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. I. Liikanen, V. Monsurrò, L. Ahtiainen et al., “Induction of interferon pathways mediates in vivo resistance to oncolytic adenovirus,” Molecular Therapy, vol. 19, no. 10, pp. 1858–1866, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. G. J. Bauerschmitz, J. T. Lam, A. Kanerva et al., “Treatment of ovarian cancer with a tropism modified oncolytic adenovirus,” Cancer Research, vol. 62, no. 5, pp. 1266–1270, 2002. View at Scopus
  32. A. Hemminki, I. Dmitriev, B. Liu, R. A. Desmond, R. Alemany, and D. T. Curiel, “Targeting oncolytic adenoviral agents to the epidermal growth factor pathway with a secretory fusion molecule,” Cancer Research, vol. 61, no. 17, pp. 6377–6381, 2001. View at Scopus
  33. A. Kanerva, M. Wang, G. J. Bauerschmitz et al., “Gene transfer to ovarian cancer versus normal tissues with fiber-modified adenoviruses,” Molecular Therapy, vol. 5, no. 6, pp. 695–704, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Hemminki, A. Kanerva, B. Liu et al., “Modulation of coxsackie-adenovirus receptor expression for increased adenoviral transgene expression,” Cancer Research, vol. 63, no. 4, pp. 847–853, 2003. View at Scopus
  35. A. Kanerva and A. Hemminki, “Modified adenoviruses for cancer gene therapy,” International Journal of Cancer, vol. 110, no. 4, pp. 475–480, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Kanerva, G. J. Bauerschmitz, M. Yamamoto et al., “A cyclooxygenase-2 promoter-based conditionally replicating adenovirus with enhanced infectivity for treatment of ovarian adenocarcinoma,” Gene Therapy, vol. 11, no. 6, pp. 552–559, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. K. Saukkonen and A. Hemminki, “Tissue-specific promoters for cancer gene therapy,” Expert Opinion on Biological Therapy, vol. 4, no. 5, pp. 683–696, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. G. J. Bauerschmitz, K. Guse, A. Kanerva et al., “Triple-targeted oncolytic adenoviruses featuring the Cox2 promoter, E1A transcomplementation, and serotype chimerism for enhanced selectivity for ovarian cancer cells,” Molecular Therapy, vol. 14, no. 2, pp. 164–174, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Pesonen, P. Nokisalmi, S. Escutenaire et al., “Prolonged systemic circulation of chimeric oncolytic adenovirus Ad5/3-Cox2L-D24 in patients with metastatic and refractory solid tumors,” Gene Therapy, vol. 17, no. 7, pp. 892–904, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. S. Pesonen, H. Helin, P. Nokisalmi et al., “Oncolytic adenovirus treatment of a patient with refractory neuroblastoma,” Acta Oncologica, vol. 49, no. 1, pp. 117–119, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Kanerva, K. R. Zinn, T. R. Chaudhuri et al., “Enhanced therapeutic efficacy for ovarian cancer with a serotype 3 receptor-targeted oncolytic adenovirus,” Molecular Therapy, vol. 8, no. 3, pp. 449–458, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. H. Wang, Z. Li, Y. Liu et al., “Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14,” Nature Medicine, vol. 17, no. 1, pp. 96–104, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Kanerva, G. V. Mikheeva, V. Krasnykh et al., “Targeting adenovirus to the serotype 3 receptor increases gene transfer efficiency to ovarian cancer cells,” Clinical Cancer Research, vol. 8, no. 1, pp. 275–280, 2002. View at Scopus
  44. J. N. Glasgow, G. J. Bauerschmitz, D. T. Curiel, and A. Hemminki, “Transductional and transcriptional targeting of adenovirus for clinical applications,” Current Gene Therapy, vol. 4, no. 1, pp. 1–14, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Wang, Z. Li, R. Yumul et al., “Multimerization of adenovirus serotype 3 fiber knob domains is required for efficient binding of virus to desmoglein 2 and subsequent opening of epithelial junctions,” Journal of Virology, vol. 85, no. 13, pp. 6390–6402, 2011. View at Scopus
  46. O. Hemminki, G. Bauerschmitz, S. Hemmi et al., “Oncolytic adenovirus based on serotype 3,” Cancer Gene Therapy, vol. 18, no. 4, pp. 288–296, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Ranki, L. Kangasniemi, P. Ahokas, et al., “Preclinical and clinical evaluation of oncolytic immunotherapy with Ad5/3-E2F1-Delta 24-GMCSF (CGTG-602), a GM-CSF producing adenovirus targeted to tumors on four levels,” Molecular Therapy, vol. 20, pp. S36–S36, 2012.
  48. I. Diaconu, V. Cerullo, M. L. M. Hirvinen et al., “Immune response is an important aspect of the antitumor effect produced by a CD40L-encoding oncolytic adenovirus,” Cancer Research, vol. 72, no. 9, pp. 2327–2338, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Westberg, A. Sadeghi, E. Svensson, et al., “Treatment efficacy and immune stimulation by AdCD40L gene therapy of spontaneous canine malignant melanoma,” Journal of Immunotherapy, vol. 36, no. 6, pp. 350–358, 2013. View at Publisher · View at Google Scholar
  50. J. D. Dias, O. Hemminki, I. Diaconu et al., “Targeted cancer immunotherapy with oncolytic adenovirus coding for a fully human monoclonal antibody specific for CTLA-4,” Gene Therapy, vol. 19, no. 10, pp. 988–998, 2012. View at Publisher · View at Google Scholar
  51. T. Hakkarainen, M. Rajecki, M. Sarparanta et al., “Targeted radiotherapy for prostate cancer with an oncolytic adenovirus coding for human sodium iodide symporter,” Clinical Cancer Research, vol. 15, no. 17, pp. 5396–5403, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Rajecki, M. Sarparanta, T. Hakkarainen et al., “SPECT/CT imaging of hNIS -expression after intravenous delivery of an oncolytic adenovirus and131I,” PLoS ONE, vol. 7, no. 3, Article ID e32871, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. K. N. Barton, H. Stricker, M. A. Elshaikh et al., “Feasibility of adenovirus-mediated hnis gene transfer and 131 i radioiodine therapy as a definitive treatment for localized prostate cancer,” Molecular Therapy, vol. 19, no. 7, pp. 1353–1359, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Rajecki, T. Af Hällström, T. Hakkarainen et al., “Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation,” International Journal of Cancer, vol. 125, no. 10, pp. 2441–2449, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. I. Liikanen, J. D. Dias, P. Nokisalmi et al., “Adenoviral E4orf3 and E4orf6 proteins, but not E1B55K, increase killing of cancer cells by radiotherapy in vivo,” International Journal of Radiation Oncology Biology Physics, vol. 78, no. 4, pp. 1201–1209, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. P. Nokisalmi, M. Rajecki, S. Pesonen et al., “Radiation-induced upregulation of gene expression from adenoviral vectors mediated by DNA damage repair and regulation,” International Journal of Radiation Oncology Biology Physics, vol. 83, no. 1, pp. 376–384, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Raki, A. Kanerva, A. Ristimaki et al., “Combination of gemcitabine and Ad5/3-Δ24, a tropism modified conditionally replicating adenovirus, for the treatment of ovarian cancer,” Gene Therapy, vol. 12, no. 15, pp. 1198–1205, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. M. Raki, M. Särkioja, R. A. Desmond et al., “Oncolytic adenovirus Ad5/3-Δ24 and chemotherapy for treatment of orthotopic ovarian cancer,” Gynecologic Oncology, vol. 108, no. 1, pp. 166–172, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. V. Cerullo, I. Diaconu, L. Kangasniemi et al., “Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus,” Molecular Therapy, vol. 19, no. 9, pp. 1737–1746, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Jiang, C. Gomez-Manzano, H. Aoki et al., “Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death,” Journal of the National Cancer Institute, vol. 99, no. 18, pp. 1410–1414, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. F. J. Zemp, B. A. McKenzie, X. Lun, et al., “Resistance to oncolytic myxoma virus therapy in nf1(-/-)/trp53(-/-) syngeneic mouse glioma models is independent of anti-viral type-I interferon,” PLoS ONE, vol. 8, Article ID e65801, 2013. View at Publisher · View at Google Scholar
  62. M. Moerdyk-Schauwecker, N. R. Shah, A. M. Murphy, et al., “Resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus: role of type I interferon signaling,” Virology, vol. 436, no. 1, pp. 221–234, 2013. View at Publisher · View at Google Scholar
  63. T. Muster, J. Rajtarova, M. Sachet et al., “Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants,” International Journal of Cancer, vol. 110, no. 1, pp. 15–21, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. N. Casares, M. O. Pequignot, A. Tesniere et al., “Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death,” Journal of Experimental Medicine, vol. 202, no. 12, pp. 1691–1701, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Obeid, A. Tesniere, F. Ghiringhelli et al., “Calreticulin exposure dictates the immunogenicity of cancer cell death,” Nature Medicine, vol. 13, no. 1, pp. 54–61, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. L. Galluzzi, L. Senovilla, L. Zitvogel, and G. Kroemer, “The secret ally: immunostimulation by anticancer drugs,” Nature Reviews Drug Discovery, vol. 11, no. 3, pp. 215–233, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. L. Zitvogel, O. Kepp, and G. Kroemer, “Immune parameters affecting the efficacy of chemotherapeutic regimens,” Nature Reviews Clinical Oncology, vol. 8, no. 3, pp. 151–160, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. A. Hemminki, “From molecular changes to customised therapy,” European Journal of Cancer, vol. 38, no. 3, pp. 333–338, 2002. View at Publisher · View at Google Scholar · View at Scopus
  69. J. R. Brahmer, S. S. Tykodi, L. Q. Chow, et al., “Safety and activity of anti-PD-L1 antibody in patients with advanced cancer,” The New England Journal of Medicine, vol. 366, pp. 2455–2465, 2012. View at Publisher · View at Google Scholar
  70. S. L. Topalian, F. S. Hodi, J. R. Brahmer, et al., “Safety, activity, and immune correlates of anti-PD-1 antibody in cancer,” The New England Journal of Medicine, vol. 366, pp. 2443–2454, 2012. View at Publisher · View at Google Scholar
  71. W. Yu and H. Fang, “Clinical trials with oncolytic adenovirus in China,” Current Cancer Drug Targets, vol. 7, no. 2, pp. 141–148, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. R. H. I. Andtbacka, F. A. Collichio, T. Amatruda, et al., “OptiM: a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma,” in Proceedings of the ASCO Annual Meeting, 2013.