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Thunder and Lightning: Immunotherapy and Oncolytic Viruses Collide

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1 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 (June 2011) DOI: /mt Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions

2 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  , DOI: ( /mt ) Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions

3 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  , DOI: ( /mt ) Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions


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