OVs and their effect on the solid tumor microenvironment
| Therapy | Virus type | Deletion/payloads | Effect on TME | Cancer models | Reference |
| VACV ΔF4L∆J2R | Vaccinia virus (double stranded DNA genome) | F4L and J2R deletions. | Tumor‐specific CD8+ T cells upregulation. | Bladder cancer | Potts et al20 |
| VVΔTKΔN1L | TK and N1L deletion. | Increased intratumoral CD4+ and CD8+T cells; Increased systemic NK cells; Neutrophil accumulation; increased IL-α, IL1-β and GCSF. | Lung cancer; Pancreatic cancer | Ahmed et al23 | |
| VVΔTKΔN1L-IL21 | TK and N1L deletion; IL-21 payload. | Increased I.T CD8+T cell and CD8+ TCM; Enhanced circulating NK cells; Macrophage polarization to M1. | Pancreatic cancer; | Marelli et al34 | |
| vvDD-IL-2-FPTM/FG/RG | TK and VGF deletion; membrane-bound IL-2 payload. | TNF-α; increased CD4+Foxp3–, CD8+IFN-γ+ T cells, decreased PD-1+CTLA-4+CD8+, PD-1+Tim-3+CD8+, PD-1+TIGIT+CD8+, and PD-1+LAG-3+CD8+ T cells. | Ovarian cancer ; Lung cancer; Colon cancer | Liu et al29 | |
| vvCCL5 | Western reserve strain, TK and VGF gene deletions, CCL5 expression in TK under p7.5 promoter. | Increased levels of CD4+ T cells, DC (CD11c+) and NK cells; Increased IL-4 and IL-5 expression. | Colon cancer | Li et al38 | |
| vvTK-IL-36γ, vvDD-IL-36γ, vvTD-IL-36γ | Insertion of an active form of IL-36γ into three VV backbones with different tumor selectivity and oncolytic activities. | Increased levels of tumor antigen-specific CD4+ and CD8+ T cells. | Colon cancer | Yang et al35 | |
| GLV-1h68 | Renilla luciferase Aequoria-GFP fusion protein, β-galactosidase and β-glucoronidase inserted into F14.5 L, J2R (TK) and A56R loci of Lister strain virus. | Increased IFN-γ, IP-10, MCP-1, MCP-3, MCP-5, RANTES and TNF-γ; A greater infiltration of macrophages and NK cells. | Colorectal cancer | Ehrig et al41 | |
| GLV-1h107, GLV-1h108, GLV-1h109 | scAb GLAF-1 inserted into the J2R (TK) locus under SE, SEL, and SL promoters (respectively) in a Lister strain virus. | Decreased microvessel density. | Lung cancer | Frentzen et al95 | |
| LIVP1.1.1 | A less virulent wild-type isolate of a strongly replicating LIVP (Lister) strain. | CD11b+ ly6G+ MDSCs recruitment, enhanced iNOS expression; higher production of NO. | Colon cancer | Kilinc et al61 | |
| VV.HPGD | Expression of HPGD from TK deleted Western Reserve strain. | Induction of a more rapid and robust reduction in MDSC and TReg. | Renca tumor; Colorectal cancer | Hou et al64 | |
| OVV-CXCR4-A-mFc | Expression of a CXCR4 antagonist from a TK-VGF-deleted Western reserve strain virus. | Destruction of I.T microvessels, lower accumulation of circulating endothelial progenitor cells and neutrophils/granulocytic-MDSCs, enhanced vaccinia-mediated activation of antitumor antibody responses. | Breast cancer | Gil et al65 | |
| EphA2-TEA-VV | vvDD armed with bispecific T-cell engager that bind both to human CD3 and tumor cell surface antigen EphA2. | Activation of T cells; Increased IFN-γ and IL-2 secretion. | Lung cancer | Yu et al81 | |
| JX-594 | Disruption of the viral TK gene and expression of the hGM-CSF and β-gal transgenes under control of the synthetic early-late and p7.5 promoters in the Wyeth strain virus. | Infection and transgene expression in tumor cells and VEGF- and FGF-2–activated human endothelial cells. Vascular collapse. | Breast cancer | Breitbach et al; Breitbach et al88 89 | |
| mpJX-594 | Mouse-prototype JX-594. | Vascular pruning and prolong leakage in tumors; Widespread CD8+T cell dependent tumor cell killing. | Glioma | Kim et al90 | |
| GLV-1h164 | Single-chain antibody sequence for GLAF-2, an antibody directed against VEGF, inserted into Lister strain, F14.5L/J2R/A56R-deleted virus. | Inhibition of vascularization. | Breast cancer | Gholami et al96 | |
| VVleptin | Leptin-armed VV WR strain with TK deletion. | Leptin-induced metabolic support allows immune cells to be polyfunctional, proliferative, and mediate tumor control; decreased TRegs; increased KLRG1hiCD127+ memory precursors. | Melanoma | Rivadeneira et al106 | |
| VVhEA | Lister strain, TK deletion. Armed with endostatin-angiostatin fusion gene. | Inhibition of angiogenesis; Reversal of VEGF-induced cancer-associated systemic syndrome. | Pancreatic cancer | Tysome et al91 | |
| HSV1716 | Herpes simplex virus (double stranded DNA genome) | Deletion in the RL1 genes encoding ICP34.5. | Increased CD11b+ Ly6C+ monocytes, CD11b+, LY6G+ neutrophils, CD3+ T cells, and CD8+ cytotoxic T cells; reduced TRegs; TAMs reprogramming. | Breast cancer | Kwan et al47 |
| Deletion or mutation of the RL1 gene. | An early influx of immune cells, mainly of CD4+ T cells, NK cells, and macrophages. | Melanoma | Miller and Fraser51 | ||
| G207 | Deletions of both γ34.5 loci and a LacZ insertion disabling the UL39 gene. | Increase GADD34 expression in hypoxic cells. | Glioblastoma | Aghi et al98 | |
| TVEC (HSV-GM-CSF) | Deletion of the ICP34.5 and ICP47 genes. Insertion of GM-CSF. | Control of M1/M2 ratios MART-1 specific CD8+ T cell accumulation, TReg and MDSC decreased. | pancreatic cancer Melanoma | Liu et al Kohlhapp and Kaufman15 44 | |
| JS1/34.5−/47−/GM-CSF | ICP34.5 and ICP47 gene deletion; insertion of human or mouse GM-CSF. | Increased MHC I expression. | Breast cancer | Liu et al29 | |
| G47Δ-mIL12 | Deletion of α47 and γ34.5 genes and insertion of LacZ into ICP6; Insertion of mouse IL-12 into ICP6 gene. | Increase CD45+ immune cells and CD8+ T cells; macrophages infiltration, granulocytic and monocytic MDSC reduction, TReg reduction, DC trafficking to spleen. | Triple-negative breast cancer | Ghouse et al32 | |
| G47Δ-mIL12 | Deletion of α47 and γ34.5 genes and insertion of LacZ into ICP6; Insertion of mouse IL-12 into ICP6 gene. | Reduction of TRegs, stimulation of Th1-type immunity, T cell mediated survival advantage; inhibition of tumor angiogenesis. | Glioblastoma | Cheema et al69 | |
| VAE | γ34.5 and ICP6 deleted HSV-1 carrying the endostatin–angiostatin fusion gene. | Reduced microvessel density. | Glioblastoma | Zhang et al92 | |
| VSV | Vesicular stomatitis virus (negative-strand RNA genome) | - | Production of IL-28; Recruitment of CD11b+ GR1+ cells and plasmacytoid DC; Sensitized tumors to NK cell recognition and killing. | Melanoma | Wongthida et al54 |
| Reduces CD31 expression; destruction of tumor vasculature. | Colon cancer | Breitbach et al89 | |||
| Infection and killing of hypoxic cancer cells. | Glioblastoma | Connor et al99 | |||
| CXCL1 and CXCL5 activation; Loss of blood flow to the interior of the tumor induced by neutrophil accumulation. | Colon cancer | Breitbach et al57 | |||
| Viral transduced MDSCs can switch from the M2 phenotype to M1. | Colon cancer | Eisenstein et al63 | |||
| Generalized T-cell activation; Increased IFN-γ. | Mesothelioma | Willmon et al60 | |||
| rVSV-UL141 | VSV expressing cytomegalovirus UL141 to downregulate CD155 | Inhibition of NK recruitment; Decreased I.T accumulations of NK and NKT. | Hepatocellular carcinoma | Altomonte et al56 | |
| VSV-IFNβ | VSV expressing the IFN-β gene | Stimulation of NK, cytotoxic T cells and DC activity. | Cervical cancer; Mammary adenocarcinoma; Prostatic cancer | Obuchi et al36 | |
| Reovirus | Reovirus (double-stranded RNA genome) | Combination with surgery | Increased CD69a and tetherin expression and IFIT1 mRNA expression in NK cells; Activation of NK cells. | Colorectal cancer | El-Sherbiny et al52 |
| Reduced SLC2A1, ABCB1, MMP2, twist family bHLH transcription factor 1, and VEGFA expression in tumor cells; downregulation of HIF-1α. | Lung cancer | Hotani et al100 | |||
| Inhibition of suppressive activity of MDSCs; increased IFN-α, IFN-β, IL-6, and IL-12β expression. | Melanoma | Katayama et al62 | |||
| MeV and MuV | Paramyxo viruses (negative-strand RNA genomes) | Induction of macrophage to an anti-tumor M1 phenotype. | Breast cancer | Tan et al46 | |
| MV-aCTLA-4; MV-aPD-L1 | Measles virus (negative-strand RNA genomes) | MV Edmonston strain encoding antibodies against CTLA-4 or PD-L1. | Increased in CD3+ T cells; decreased in TRegs; Increased CD8+/TReg ratios and IFN-γ expression. | Melanoma | Engeland et al72 |
| MV-hE:A and MV-mE:A | MV Edmonston strain encoding endostatin and angiostatin | Inhibition of angiogenic factors and blood vessel formation | Medulloblastoma | Hutzen et al93 | |
| MV-m-uPA MV-h-uPA | MV Edmonston strain expressing murine or human uPAR. | Simultaneous infection of stromal and tumor cells; Upregulation of Fez1 and Pycard; Downregulation of DLL-4, Angiopoietin 2, PECAM, Tie-1, and FOS EGR2, CREB-5, IL-6, Map2K1, CCL22, TIMD4 and CCL19. | Breast cancer | Jing et al79 | |
| Ad5-D24-RGD | E1A deletion; insertion of RGD-4C in the Ad5 virus. Combination with ECM-degrading proteases relaxin, elastase and MME. | Control of M1/M2 ratios; ECM remodeling. | Lung cancer | Lavilla-Alonso et al42 | |
| Ad5/3-Δ24aCTLA4 | Insertion of the cDNA sequence for an IgG2-type anti-CTLA4mAb to E3gp19K region of E1A-deleted Ad5/3 chimera (serotype 3 knob). | Inhibition of TRegs and increased CD8+/TReg ratios; Increased T cell activity. | Lung cancer; Ovarian cancer; Prostate cancer; Head and neck squamous cell carcinoma | Dias et al74 | |
| Ad-TD-nsIL-12 | Ad5 with E1ACR2, E1B19K and E3gp19K gene deletions encoding non-secreting IL-12. | Increased CD3+CD4+T cell infiltration; Reduced expression of inflammatory cytokines. | Pancreatic cancer | Wang et al13 | |
| AdwtRGD-PH20 | AdV with a fiber RGD motif expressing soluble PH20 under the control of the major late promoter. | Decrease in tumor HA levels and wider areas of virus replication. | Prostate carcinoma | Guedan et al78 | |
| AdCMVdelta24 | 24 bp deletion in E1A. | Decreased tumor-infiltrating TRegs and increased IFNγ-producing CD8+ T cells; Reprogrammed TRegs from an immunosuppressive to a stimulatory state. | Glioblastoma | Qiao et al66 | |
| oAd/IL12/GM-RLX | E1B19K and E1B55K deleted AdV expressing relaxin, IL-12, and GM-CSF; combination with αPD-1. | Enhanced drug distribution; A higher level of I.T T cell infiltration (CD4+ and CD8+) and IFN-γ expression; Attraction of activated T cells and infiltration into poorly immunogenic tumors. | Gastric cancer; Pancreatic cancer | Jung et al77 | |
| ICO15K-FBiTE | Deletion of 24 bp E1A region, RGD-modified fiber domain, expression of FAP-CD3ɛ- targeting BiTE. | Activation and proliferation of T cells; CAF targeting; Increased tumor T cell retention and accumulation. | Vulval epidermoid carcinoma; Lung cancer; Pancreatic cancer | de Sostoa et al82 | |
| EnAd-CMV/SA-FAP-BiTE | Group B adenovirus Enadenotucirev expressing αFAP/αCD3 BiTE. | T cell activation and killing of autologous CAFs; Depletion of FAP+ fibroblasts ; Increased IL-17A, IL-17F, IL-22, IFN-γ, and IL-10 expression; Repolarization of M2 ascites macrophages. | Colorectal cancer; Lung cancer | Freedman et al83 | |
| OBP301 | Human telomerase reverse transcriptase promoter element drives the expression of E1A and E1B genes linked with an internal ribosomal entry sequence. | Increased IFN-γ expression; Inhibition of angiogenesis. | Colorectal cancer | Ikeda et al87 | |
| rAd-E1A | Expression of E1A tumor suppressor gene. | Induction of tumor cell apoptosis; Downregulation of VEGF and CD34; Reduced tumor blood vessel formation. | Hepatocellular carcinoma | Ye et al86 | |
| EnAd‐CMV‐EpCAM BiTE | Group B adenovirus Enadenotucirev expressing EpCAM BiTE, regulate by CMV promoter. | Strong T‐cell activation; Depletion of EpCAM‐positive cells. | Ovarian cancer | Freedman et al83 | |
| EnAd-CMV-BiTE/TriTE | BiTEs were CD3ε scFv, CD206-targeting nanobody or a folate receptor β-targeting scFv. Addition of anti-CD28 scFv or a second anti-CD3 scFv. | Activation and expansion of CD4+ and CD8+ T cells; Increased CD11b+CD64+ cells; Increased IFN-γ expression. | Colorectal cancer | Scott et al48 | |
| CNHK500-mE | E1A gene controlled by the hTERT promoter and the E1b promoter is replaced by HRE; expression of endostatin. | Anti-angiogenic. | Hepatocyte cancer; Pancreatic cancer; Lung cancer; Breast cancer; Nasopharyngeal cancer; Cervical cancer; Gastric cancer | Su et al94 | |
| CVB3 | Coxsackie virus (positive-strand RNA genome) | --- | Tumor cells express calreticulin and secreted ATP as well HMGB1; NK and granulocyte recruitment. | Lung cancer | Miyamoto et al53 |
| PVSRIPO | Poliovirus (positive-strand RNA genome) | Poliovirus genome carrying a heterologous IRES from HRV2. | Induction of extensive neutrophil infiltration; DC and T cell infiltration and activation. | Breast cancer; Prostate cancer | Holl et al58 |
| NDV-αCTLA4 | Newcastle disease virus (negative-strand RNA genome) | NDV expressing anti-CTLA4 scFv. | TReg inhibition; Increased CD8+/TReg ratios. | Melanoma | Vijayakumar et al73 |
AdV, adenovirus; BiTE, bispecific T cell engagers; CAFs, cancer associated fibroblasts ; DC, dendritic cell ; ECM, extracellular matrix ; EnAd, enadenotucirev; FAP, fibroblast activation protein; GM-CSF, granulocyte-macrophage colony-stimulating factor ; HMGB1, high mobility group box 1 protein; HSV, herpes virus ; IFN, interferon; IL, interleukin; IRES, internal ribosomal entry site; I.T, intratumoral; mAbs, monoclonal antibodies ; MDSC, myeloid derived suppressor cells; MeV, measles virus ; MHC, major histocompatibility complex; mRNA, messenger RNA; MuV, mumps viruses; NDV, Newcastle disease virus ; NK, natural killer; NO, nitric oxide; OVs, oncolytic viruses ; PD-1, programmed cell death protein-1; PD-L1, programmed death ligand-1; TME, tumor microenvironment ; TNF, tumor necrosis factor; TReg, regulatory T cell ; VGF, viral growth factor ; VSV, vesicular stomatitis virus ; VV, vaccinia virus ; WR, Western Reserve .