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Table 8 Strategies to arm oncolytic viruses for cancer immunotherapy

From: Combination strategies to maximize the benefits of cancer immunotherapy

The anti-cancer immunity cycle Transgenes to arm OVs and enhance cancer immunotherapy Example transgenes
Step 1. Cancer cell death and antigen release Molecules inducing immunogenic cell death Type I IFN, TNF╬▒, TRAIL
Step 2. Antigen presentation Tumor-associated antigens, cancer vaccine, chemokine Truncated CD19, cancer vaccine, GM-CSF
Step 3. Priming and activation Checkpoint inhibitors, co-stimulatory molecules, immunostimulatory cytokines Anti-CTLA4 miniantibody, anti-PD1, IL-2, IL15, OX40L, 4-1BBL
Step 4. T cell trafficking Molecules targeting tumor vasculature, VEGF/VEGFR inhibitor, endostatin,
Step 5. Infiltration into tumors Chemokines to attract T cells; molecules targeting tumor stroma and matrix degradation CXCL9, CXCL10 CXCL11, CCL2, CCL5, hyaluronidase, collagenase, MMP-9
Step 6. Recognition of tumor cells by T cells Bi-specific T cell engager (BiTE) BiTE targeting CD3 and CD19, BiTE targeting EpCAM and CD3
Step 7. Killing of cancer cells Checkpoint inhibitors, co-stimulatory molecules, immunostimulatory cytokines, molecules targeting TME metabolism, molecules targeting or depleting inhibitory immune cells Anti-CTLA4 miniantibody, anti-PD1, IL-2, IL15, OX40L, 4-1BBL, CD39/CD73/A2aR, IDO inhibitors