Designing, engineering and testing of targeted strains of vaccinia virus to act as oncolytic agents for the treatment of cancer, with special emphasis on;
Enhancing systemic delivery, especially in the face of anti-viral immunity.
Enhancing early viral spread in the tumor microenvironment.
Optimizing viral interaction with the host immune response
Development of novel transgenes to be expressed from oncolytic virus vectors, especially constructs capable of inducing a targeted and localized bystander killing effect.
Effects of exogenously regulating oncolytic vector transgene function.
Effects of combining oncolytic viruses with approved and experimental therapies, especially;
Immune cell therapies, both as combination cancer therapies and the use of immune cells as carrier vehicles to deliver viruses to tumors.
Chemotherapies, including taxols and cisplatin.
Tyrosine Kinase Inhibitors.
Monoclonal antibodies, especially anti-immune checkpoint inhibitors.
Examination of host-pathogen interactions.
Use and development of pre-clinical imaging tools (especially optical imaging) to non-invasively examine molecular events in vivo.
- Hou W, Sampath P, Rojas JJ, Thorne SH. Oncolytic Virus-Mediated Targeting of PGE2 in the Tumor Alters the Immune Status and Sensitizes Established and Resistant Tumors to Immunotherapy.. Cancer Cell. 2016 Jul 11;30(1):108-19. doi: 10.1016/j.ccell.2016.05.012. PubMed PMID: 27374223;
- Thorne SH. Virus fuels NK cell killing of leukemia.. Blood. 2016 May 26;127(21):2509. doi: 10.1182/blood-2016-03-704247. PubMed PMID: 27231392;
- Rojas JJ, Sampath P, Bonilla B, Ashley A, Hou W, Byrd D, Thorne SH. Manipulating TLR Signaling Increases the Anti-tumor T Cell Response Induced by Viral Cancer Therapies.. Cell Rep. 2016 Apr 12;15(2):264-73. doi: 10.1016/j.celrep.2016.03.017. PubMed PMID: 27050526;
- Ilkow CS, Marguerie M, Batenchuk C, Mayer J, Ben Neriah D, Cousineau S, Falls T, Jennings VA, Boileau M, Bellamy D, Bastin D, de Souza CT, Alkayyal A, Zhang J, Le Boeuf F, Arulanandam R, Stubbert L, Sampath P, Thorne SH, Paramanthan P, Chatterjee A, Strieter RM, Burdick M, Addison CL, Stojdl DF, Atkins HL, Auer RC, Diallo JS, Lichty BD, Bell JC. Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity. Nat Med. 2015 May;21(5):530-6. doi: 10.1038/nm.3848. Epub 2015 Apr 20. [link]
- Zou Y, Li F, Hou W, Sampath P, Zhang Y, Thorne SH. Manipulating the expression of chemokine receptors enhances delivery and activity of cytokine-induced killer cells. Br J Cancer. 2014 Apr 15;110(8):1992-9. doi: 10.1038/bjc.2014.140. Epub 2014 Mar 18. [link]
- Hou W, Chen H, Rojas J, Sampath P, Thorne SH. Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF. Int J Cancer. 2014 Sep 1;135(5):1238-46. doi: 10.1002/ijc.28747. Epub 2014 Feb 18. [link]
- Chen H, Sampath P, Hou W, Thorne SH. Regulating cytokine function enhances safety and activity of genetic cancer therapies. Mol Ther. 2013 Jan;21(1):167-74. doi: 10.1038/mt.2012.225. Epub 2012 Nov 13. [link]
- Sampath P, Li J, Hou W, Chen H, Bartlett DL, Thorne SH. Crosstalk between immune cell and oncolytic vaccinia therapy enhances tumor trafficking and antitumor effects. Mol Ther. 2013 Mar;21(3):620-8. doi: 10.1038/mt.2012.257. Epub 2012 Dec 11. [link]
- Wang LC, Lynn RC, Cheng G, Alexander E, Kapoor V, Moon EK, Sun J, Fridlender ZG, Isaacs SN, Thorne SH, Albelda SM. Treating tumors with a vaccinia virus expressing IFNβ illustrates the complex relationships between oncolytic ability and immunogenicity. Mol Ther. 2012 Apr;20(4):736-48. doi: 10.1038/mt.2011.228. Epub 2011 Oct 18. [link]
- MacTavish H, Diallo JS, Huang B, Stanford M, Le Boeuf F, De Silva N, Cox J, Simmons JG, Guimond T, Falls T, McCart JA, Atkins H, Breitbach C, Kirn D, Thorne S, Bell JC. Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors. PLoS One. 2010 Dec 30;5(12):e14462. doi: 10.1371/journal.pone.0014462. [link]
- Contag CH, Sikorski R, Negrin RS, Schmidt T, Fan AC, Bachireddy P, Felsher DW, Thorne SH. Definition of an enhanced immune cell therapy in mice that can target stem-like lymphoma cells. Cancer Res. 2010 Dec 1;70(23):9837-45. doi: 10.1158/0008-5472.CAN-10-2650. Epub 2010 Oct 8. [link]
University of Pittsburgh
Department of Cell Biology
Hillman Cancer Center 1.46e