Display options
Cite
Beug ST, Pichette SJ, St-Jean M, et al. Combination of IAP Antagonists and TNF-α-Armed Oncolytic Viruses Induce Tumor Vascular Shutdown and Tumor Regression. Mol Ther Oncolytics. 2018;10:28-39doi: 10.1016/j.omto.2018.06.002.
Beug, S. T., Pichette, S. J., St-Jean, M., Holbrook, J., Walker, D. E., LaCasse, E. C., & Korneluk, R. G. (2018). Combination of IAP Antagonists and TNF-α-Armed Oncolytic Viruses Induce Tumor Vascular Shutdown and Tumor Regression. Molecular therapy oncolytics, 1028-39. https://doi.org/10.1016/j.omto.2018.06.002
Beug, Shawn T, et al. "Combination of IAP Antagonists and TNF-α-Armed Oncolytic Viruses Induce Tumor Vascular Shutdown and Tumor Regression." Molecular therapy oncolytics vol. 10 (2018): 28-39. doi: https://doi.org/10.1016/j.omto.2018.06.002
Beug ST, Pichette SJ, St-Jean M, Holbrook J, Walker DE, LaCasse EC, Korneluk RG. Combination of IAP Antagonists and TNF-α-Armed Oncolytic Viruses Induce Tumor Vascular Shutdown and Tumor Regression. Mol Ther Oncolytics. 2018 Jun 21;10:28-39. doi: 10.1016/j.omto.2018.06.002. eCollection 2018 Sep 28. PMID: 30101187; PMCID: PMC6076221.
Copy Download .nbib Format: NLM
Share it on

Mol Ther Oncolytics. 2018 Jun 21;10:28-39. doi: 10.1016/j.omto.2018.06.002. eCollection 2018 Sep 28.

Combination of IAP Antagonists and TNF-α-Armed Oncolytic Viruses Induce Tumor Vascular Shutdown and Tumor Regression.

Molecular therapy oncolytics

Shawn T Beug, Stephanie J Pichette, Martine St-Jean, Janelle Holbrook, Danielle E Walker, Eric C LaCasse, Robert G Korneluk

Affiliations

  1. Apoptosis Research Center, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
  2. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada.

PMID: 30101187 PMCID: PMC6076221 DOI: 10.1016/j.omto.2018.06.002

Abstract

Smac mimetic compounds (SMCs) are anti-cancer drugs that antagonize Inhibitor of Apoptosis proteins, which consequently sensitize cancer cells to death in the presence of proinflammatory ligands such as tumor necrosis factor alpha (TNF-α). SMCs synergize with the attenuated oncolytic vesicular stomatitis virus (VSVΔ51) by eliciting an innate immune response, which is dependent on the endogenous production of TNF-α and type I interferon. To improve on this SMC-mediated synergistic response, we generated TNF-α-armed VSVΔ51 to produce elevated levels of this death ligand. Due to ectopic expression of TNF-α from infected cells, a lower viral dose of TNF-α-armed VSVΔ51 combined with treatment of the SMC LCL161 was sufficient to improve the survival rate compared to LCL161 and unarmed VSVΔ51 co-therapy. This improved response is attributed to a bystander effect whereby the spread of TNF-α from infected cells leads to the death of uninfected cells in the presence of LCL161. In addition, the treatments induced vascular collapse in solid tumors with a concomitant increase of tumor cell death, revealing another mechanism by which cytokine-armed VSVΔ51 in combination with LCL161 can kill tumor cells. Our studies demonstrate the potential for cytokine-engineered oncolytic virus and SMCs as a new combination immunotherapy for cancer treatment.

Keywords: SMC; Smac mimetic compound; Smac mimetics; TNF-α; VSV; cIAP1/cIAP2; cancer; cellular inhibitor of apoptosis 1/2; immunotherapy; oncolytic virus; tumor necrosis factor alpha; vascular collapse; vesicular stomatitis virus

References

  1. Apoptosis. 2007 Sep;12(9):1543-68 - PubMed
  2. Hum Gene Ther Clin Dev. 2013 Dec;24(4):174-81 - PubMed
  3. Hum Gene Ther. 2015 Mar;26(3):134-44 - PubMed
  4. Biochem Pharmacol. 2012 Aug 1;84(3):268-77 - PubMed
  5. J Biol Chem. 2010 Dec 24;285(52):40612-23 - PubMed
  6. Trends Immunol. 2012 Nov;33(11):535-45 - PubMed
  7. Int J Hyperthermia. 2008 May;24(3):193-203 - PubMed
  8. Head Neck. 2014 Nov;36(11):1619-27 - PubMed
  9. Nat Med. 2016 Dec;22(12):1411-1420 - PubMed
  10. Nat Rev Cancer. 2014 Aug;14(8):559-67 - PubMed
  11. Cancer Gene Ther. 2013 Jan;20(1):46-56 - PubMed
  12. Pediatr Blood Cancer. 2012 Apr;58(4):636-9 - PubMed
  13. J Immunol. 1987 Feb 1;138(3):963-74 - PubMed
  14. J Med Chem. 2006 Dec 28;49(26):7916-20 - PubMed
  15. Nat Rev Immunol. 2012 Dec;12(12):833-44 - PubMed
  16. Nat Genet. 2007 Nov;39(11):1397-402 - PubMed
  17. Nat Biotechnol. 2014 Feb;32(2):182-90 - PubMed
  18. J Surg Oncol. 2014 Mar;109(4):338-47 - PubMed
  19. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11778-83 - PubMed
  20. Nat Rev Cancer. 2009 May;9(5):361-71 - PubMed
  21. Biochem J. 2009 Jan 1;417(1):149-60 - PubMed
  22. Mol Ther Oncolytics. 2016 Feb 17;3:16001 - PubMed
  23. Cancer Gene Ther. 2012 Apr;19(4):238-46 - PubMed
  24. Mol Ther. 2011 May;19(5):886-94 - PubMed
  25. Cancer Cell. 2003 Oct;4(4):263-75 - PubMed
  26. J Med Chem. 2004 Aug 26;47(18):4417-26 - PubMed
  27. Oncologist. 2006 Apr;11(4):397-408 - PubMed
  28. Oncotarget. 2011 Oct;2(10):739-51 - PubMed
  29. Blood. 2014 Apr 17;123(16):2562-72 - PubMed
  30. Nat Cell Biol. 2006 Apr;8(4):398-406 - PubMed
  31. Mol Ther. 2012 Sep;20(9):1791-9 - PubMed
  32. Mol Ther. 2011 Jun;19(6):1008-16 - PubMed
  33. Eur J Cancer. 1991;27(7):856-63 - PubMed
  34. EMBO Rep. 2015 Jun;16(6):719-27 - PubMed
  35. Clin Cancer Res. 2015 Nov 15;21(22):5030-6 - PubMed
  36. Nat Rev Drug Discov. 2012 Feb 01;11(2):109-24 - PubMed
  37. Cancer Chemother Pharmacol. 1989;23(3):186-91 - PubMed
  38. Ann Surg Oncol. 2012 Feb;19(2):627-35 - PubMed
  39. Leukemia. 2012 Aug;26(8):1870-8 - PubMed
  40. Cancer Res. 2009 Oct 1;69(19):7729-38 - PubMed
  41. Laryngoscope. 2007 Feb;117(2):210-4 - PubMed
  42. Hum Gene Ther Clin Dev. 2016 Sep;27(3):111-22 - PubMed
  43. Cancer Res. 2009 Oct 1;69(19):7713-20 - PubMed
  44. J Clin Oncol. 1987 Nov;5(11):1816-21 - PubMed
  45. Nat Commun. 2017 Feb 15;8: - PubMed
  46. Gynecol Oncol. 2014 Jan;132(1):194-202 - PubMed
  47. Mol Cell. 2006 Apr 21;22(2):245-57 - PubMed

Publication Types