Table 2. Novel combination of VSV with other drugs against cancer (reported 2012–2017).
↑increase; ↓decrease.
| VSV variant | Drug name | Drug type | Ref | Designed to improve: | Observed in vitro effects | Observed in vivo effects | ||
|---|---|---|---|---|---|---|---|---|
| Onco-selectivity | Safety |
Direct
Oncotoxicity |
||||||
| VSV-ΔM51-GFP | gemcitabine | Antimetabolite antineoplastic agent | [54] | X | ↓ tumour volume in mouse PDAC xenografts | |||
| VSV-CT9-M51 and VSV-rp30 | IFN-αA/D, ribavirin and chloroquine | IFN, viral nucleoside inhibitor and quinolone respectively | [56] | X | ↓ replication, cytotoxicity and infectivity in neuronal cell cultures | ↓ neurotoxicity and ↑ survival after intracranial VSV-CT9-M51 injection in Swiss-Webster mice | ||
| VSV-GFP | NSC74859 | STAT3 inhibitor | [57] | X | X | ↓ HCC cell proliferation ↓ replication in primary human hepatocytes ↓ cytotoxicity in primary rat neurons and glial cells |
↓ toxicity and ↑ maximum tolerated dose of VSV in C57BL/6 mice | |
| VSV-ΔM51-GFP and VSV-GFP | JAK Inhibitor I | pan-JAK inhibitor | [64, 66, 68] | X | ↓ MX1 and OAS expression in resistant PDAC cell lines ↑ replication and oncolysis in resistant PDAC cell lines ↓ IRF-9, IRF-7 and OAS expression in human head and neck cancer cells ↑ infection, spread and progeny yield in human head and neck cancer cells |
|||
| VSV-ΔM51-GFP, VSV-GFP and VSV-GP | ruxolitinib | JAK1/JAK2 inhibitor | [66–69] | X | ↓ MX1, EPSTI1, XAF1 and GBP1 expression in PDAC cell lines ↑ replication and oncolysis in resistant PDAC cell lines ↓ IRF-9, IRF-7 and OAS in human head and neck cancer cells ↑ infection, spread and progeny yield in human head and neck cancer cells ↑ replication and oncolysis in ovarian cancer cell lines |
↓ tumour volume and ↑ survival in both subcutaneous and orthotopic xenograft mouse ovarian cancer models | ||
| VSV-ΔM51-GFP and VSV | TPCA-1 | IKK-β inhibitor, but we demonstrated that it also inhibits JAK1 | [66, 67, 71] | X | ↓ MX1, EPSTI1, XAF1 and GBP1 expression in PDAC cell lines ↑ replication and oncolysis in resistant PDAC cell lines ↓ MX1 and GBP1 in human glioma cells ↑ replication and oncolysis in human glioma cells |
|||
| VSV, VSV-GFP and VSV-mIFN-NIS | BMS-345541 | IKK inhibitor | [71, 72] | X | ↓ MX1 and GBP1 in human glioma cells ↑ replication and oncolysis in human glioma cells but not in myeloma cells |
|||
| VSV-GFP and VSV-mIFN-NIS | bortezomib | proteasome inhibitor | [72] | X | ↓ replication and oncolysis in myeloma cells | ↓ tumour volume and ↑ survival in myeloma mouse model | ||
| VSV | Vorinostat | HDAC inhibitor | [73] | X | ↑ NF-κB signalling ↓ IFN signalling ↑ autophagy ↑ replication ↑ oncolysis in prostate cancer cell lines |
|||
| rwt-GFP and rM51R-GFP | curcumin | Natural agent | [75] | X | ↓ NF-κB phosporylation ↓ STAT1 activation ↓ Bcl-xl expression ↑ infection ↑ oncolysis in prostate cancer cell lines |
↓ tumour volume of prostate tumours in BALB/c nude mice | ||
| VSV-Δ51-GFP and VSV-Δ51-Luc | triptolide | Natural agent | [76] | X | ↑ replication in human prostate cancer cell lines and human B-lymphoma cell line ↓ type I IFN signalling ↑ apoptosis |
↑ replication in a prostate mouse xenograft model ↓ tumour volume and ↑ survival in mammary adenocarcinoma mouse xenograft model |
||
| VSVΔ51 | colchicine | microtubule-destabilizing agent | [77] | X | ↓ type I IFN production ↑ viral spread ↑ infection-induced cytokines ↑ viral bystander effects |
↑ spread and oncolytic activity in colon cancer nude mouse model and breast cancer syngeneic mouse model | ||
| VSV-ΔM51 | Polybrene or DEAE-dextran and ruxolitinib | Polycations and JAK1/JAK2 inhibitor | [85] | X | ↑ attachment ↑ replication ↑ oncolysis of PDAC cell lines |
|||
| VSVM51R | Obatoclax or ABT-737 | BCL-2 inhibitors | [89] | X | ↑ apoptosis ↑ autophagy ↑ oncolysis |
↓ tumour volume and ↑ survival of chronic lymphocytic leukemia xenograft mouse model | ||
| VSVΔ51-GFP | LCL161 | SMAC mimetic inhibitor | [90] | X | ↑ oncolysis but no synergy with VSV | ↓ tumour volume and ↑ survival in rhabdomyosarcoma syngeneic mice | ||
| VSVM51R | sunitinib | Anti-angiogenic (inhibitor of VEGF-R and PDGF-R) | [102] | X | ↓ eIF2-α phosphorylation (substrate of PKR) ↑ replication ↑ oncolysis |
↓ tumour volume of prostate tumours in nude mice, breast tumours in immunocompetent mice and renal cell carcinoma tumours in nude mice | ||
| VSVΔ51 | ZD6126 | Vascular disrupting agent | [99] | X | ↑ oncolysis | ↑ survival of hypopharyngeal squamous cell carcinoma mouse xenograft model | ||