Thunder and Lightning: Immunotherapy and Oncolytic Viruses Collide Alan Melcher, Kelley Parato, Cliona M Rooney, John C Bell  Molecular Therapy  Volume 19, Issue 6, Pages 1008-1016 (June 2011) DOI: 10.1038/mt.2011.65 Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions

Figure 1 It takes two to tango: striking the balance between antitumor activity, and antivector immunity. (a) Immune barriers to oncolytic virus (OV) delivery/spread. (b) Antitumor immune activity. (c) Blockade/suppression of immune activity. CAR, chimeric antigen receptor; CTL, cytotoxic T lymphocyte; DC, dendritic cell; IDO, indoleamine 2,3-dioxygenase; IFN, interferon; IL, interleukin; MHC, major histocompatibility complex; NK, natural killer cell; TGF-β, transforming growth factor-β; TIL, tumor infiltrating lymphocyte; VEGF, vascular endothelial growth factor. Molecular Therapy 2011 19, 1008-1016DOI: (10.1038/mt.2011.65) Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions

Figure 2 Combining oncolytic virotherapy with tumor-specific T cells. Oncolytic virus (OV)-specific T cells could be expanded ex vivo after the second vaccination. If the individual was already exposed to the OV by vaccination or prior infection, then the T cells could be manufactured earlier. After activation, the T cells could be transduced with a retroviral vector expressing a tumor-specific chimeric antigen receptor (CAR) to redirect their specificity to a tumor antigen. The transduced cytotoxic T lymphocytes (CTLs) could then be infused after virotherapy when the tumor load would be reduced. The OV could then be used as a vaccine to induce T-cell expansion and maintain function. Molecular Therapy 2011 19, 1008-1016DOI: (10.1038/mt.2011.65) Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions