Background
Immunosuppression in the TME
Tumor cells and tumor-associated immune cells construct an immunosuppressive network
Non-immune stromal components and immunosuppression
Role of the immunosuppressive TME in outcomes of immunotherapy
Current development of oncolytic virotherapy
OV type | Genome structure | OV mutant | Genetic modification | Clinical application | Administration approach |
---|---|---|---|---|---|
HSV-1 | Double stranded DNA | T-Vec | ICP34.5 and ICP47 deletion GM-CSF insertion | Melanoma, sarcoma, head and neck cancer, breast cancer, colorectal cancer, pancreatic cancer | Intratumoral |
HF10 | UL43, UL49.5, UL55, UL56, and LAT deletion | Melanoma, breast cancer, pancreatic cancer | Intratumoral | ||
HSV1716 | ICP34.5 mutation | Late-stage pediatric cancers, melanoma, hepatocellular carcinoma, glioblastoma,mesothelioma, neuroblastoma | Intratumoral, intravenous | ||
Adenovirus | Double stranded DNA | ONYX-15 | E1B55K deletion | Pancreatic cancer, colorectal cancer, head and neck cancer, ovarian cancer | Intratumoral |
H101 | E1B55K & partial E3 deletion, | Head and neck cancer | Intratumoral | ||
LOAd703 | E1ACR2 deletion, E2F-binding sites insertion TMZ-CD40L & 4-1BBL insertion | Pancreatic cancer, melanoma | Intratumoral | ||
VCN-01 | E1ACR2 deletion, E2F-binding sites insertion, PH20 hyaluronidase insertion, RGD insertion in the fibre knob | Head and neck cancer, retinoblastoma, pancreatic cancer | Intratumoral, intravenous, intravitrous | ||
Telomelysin (OBP-301) | hTERT insertion | Solid tumors | Intratumoral | ||
ONCOS-102 | GM-CSF insertion | Peritoneal malignancies, prostate cancer | Intratumoral | ||
Vaccinia virus | Double stranded DNA | Pexa-Vec (JX-594) | thymidine kinase mutation GM-CSF, lacZ insertion | Hepatocellular carcinoma, colorectal cancer, solid tumors | Intratumoral, intravenous |
GL-ONC1 | Ruc-GFP, lacZ, gusA insertion | Head and neck cancer, ovarian cancer | Intravenous | ||
Parvovirus | Single stranded DNA | H-1PV (ParvOryx) | / | Glioblastoma, pancreatic cancer | Intratumoral, intravenous |
Reovirus | Double stranded RNA | Reolysin® (pelareorep) | / | Melanoma, breast cancer, prostate cancer, ovarian cancer, multiple myeloma, pancreatic cancer, colorectal cancer, non-small cell lung carcinoma | Intravenous |
Measles virus | Single stranded RNA | MV-NIS | Sodium-iodide symporter insertion | Multiple myeloma | Intravenous |
Coxsackie virus | Single stranded RNA | CAVATAK | / | Melanoma, breast cancer, prostate cancer, bladder cancer, non-small cell lung carcinoma | Intratumoral |
Herpes simplex virus 1 (HSV-1)
Adenovirus
Vaccinia virus (VV)
Reovirus
Measles virus (MV)
Coxsackievirus A21 (CVA21 or CAVATAK)
OVs reverse immunosuppression by modulating TME components
Activation of innate immunity under OV infection
OV infection facilitates adaptive immune responses
Genetically engineered OVs as a promising immunotherapeutic agent
Expression of immunostimulatory molecules by OVs
Expression of ICB proteins by OVs
Expression of bispecific T-cell engagers by OVs
Expression of stromal regulators by OVs
OVs in combination with immunotherapy
Combination strategy | OV type | OV mutant | Combination agent | Targeted cancer | Trial phase | Trial status | Trial No. |
---|---|---|---|---|---|---|---|
Immunotherapy | HSV-1 | T-Vec | Pembrolizumab (anti-PD1) | Melanoma | II, III | Active (not recruiting) | NCT02263508, NCT02965716 |
Pembrolizumab | Head and neck cancer | I | Active (not recruiting) | NCT02626000 | |||
Ipilimumab (anti-CTLA4) | Sarcoma | II | Recruiting | NCT03069378 | |||
Ipilimumab | Melanoma | I/II | Active (not recruiting) | NCT01740297 | |||
Ipilimumab + Nivolumab (anti-PD1) | Breast cancer | I | Recruiting | NCT04185311 | |||
Atezolizumab (anti-PD-L1) | Breast cancer, colorectal cancer | I | Recruiting | NCT03256344, NCT03802604 | |||
HF10 | Ipilimumab | Melanoma | II | Completed | NCT02272855 | ||
Nivolumab | Melanoma | II | Active (not recruiting) | NCT03259425 | |||
Adenovirus | LOAd703 | Atezolizumab | Melanoma | I/II | Recruiting | NCT04123470 | |
VCN-01 | Durvalumab (anti-PD-L1) | Head and neck cancer | I | Recruiting | NCT03799744 | ||
Telomelysin | Pembrolizumab | Advanced solid tumors | I | Recruiting | NCT03172819 | ||
ONCOS-102 | Durvalumab | Peritoneal malignancies | I/II | Recruiting | NCT02963831 | ||
Reovirus | Reolysin® | Pembrolizumab | Pancreatic cancer | II | Active (not recruiting) | NCT03723915 | |
Nivolumab | Multiple myeloma | I | Recruiting | NCT03605719 | |||
Vaccinia virus Vaccinia virus | Pexa-Vec Pexa-Vec | Ipilimumab | Advanced solid tumors | I | Recruiting | NCT02977156 | |
Immunotherapy | Durvalumab + Tremelimumab (anti-PD-L1) | Colorectal cancer | I/II | Recruiting | NCT03206073 | ||
Nivolumab | Hepatocellular carcinoma | I/II | Active (not recruiting) | NCT03071094 | |||
Coxsackie virus | CAVATAK | Pembrolizumab | Melanoma | I | Completed | NCT02565992 | |
Pembrolizumab | Non-small cell lung carcinoma, bladder cancer | I | Completed | NCT02043665 | |||
Ipilimumab | Melanoma | I | Completed | NCT02307149, NCT03408587 | |||
Pembrolizumab | Non-small cell lung carcinoma | I | Active (not recruiting) | NCT02824965 | |||
Multi-therapy | Adenovirus | LOAd703 | Atezolizumab + Gemcitabine + Nab-paclitaxel | Pancreatic cancer | I/II | Recruiting | NCT02705196 |
ONCOS-102 | Pembrolizumab + Cyclophosphamide | Melanoma | I | Active (not recruiting) | NCT03003676 | ||
Reovirus | Reolysin® | Pembrolizumab + Gemcitabine + FOLFIRI | Pancreatic cancer | I | Completed | NCT02620423 |