TABLE 1.
Clinical trials for treatment of melanoma with oncolytic viruses.
| Oncolytic Vector | System | Transgene Load//Vector Main Modifications | Selectivity | Study Phase | Combination | Ref./Number clinical trial |
|---|---|---|---|---|---|---|
| T-VEC (Imlygic, talimogene laherparepvec) | Herpes simplex (HSV-1) | GM-CSF//Deletion: ICP34.5 (blocks PKR-eIF2 pathway) and ICP47 (reduces immune activation) genes | Replication in cells with low protein kinase R (PKR) levels | I, II, III, Approved a | — | Conry et al. (2018) |
| Ib | Pembrolizumab | Ribas et al. (2017) | ||||
| Ib/III | Pembrolizumab | NCT02263508 | ||||
| Ib/II | Ipilimumab | Chesney et al. (2018) | ||||
| Pexa-Vec (JX-594, pexastimogene devacirepvec) | Vaccinia | GM-CSF and β-galactosidase//Deletion: thymidine kinase gene (promotes DNA synthesis) | Replication in cells high cellular thymidine kinase activity and active EGFR signaling | Ib/II | Anti-PD-L1 mAb (ZKAB001) | NCT04849260 |
| Telomelysin (OBP-301) | Adenovirus | E1A and E1B regions under control of the human telomerase reverse transcriptase (hTERT) promoter | Replication in cells with telomerase activity | I | — | Nemunaitis et al. (2010) |
| TILT-123 | Adenovirus | IL2 and TNF-α//D24 deletion in the E1A gene (inactivates pRB); E2F promoter | Replication in cells with high expression of E2F and with a dysregulated retinoblastoma pathway | I | TILs | NCT04217473 |
| ICOVIR-5 | Adenovirus | D24 deletion in the E1A gene (inactivates pRB); human E2F-1 promoter | Replication in cells with high expression of E2F and with a dysregulated retinoblastoma pathway | I | — | García et al. (2018) |
| LOAd703 (delolimogene mupadenorepvec) | Adenovirus | 4-1BBL and TMZ-CD40L//D24 deletion in the E1A gene (inactivates pRB) | Replication in cells with a dysregulated retinoblastoma pathway | I/II | Atezolizumab | NCT04123470 |
| ONCOS-102 (Ad5/3∆24 GMCSF, CGTG-102) | Adenovirus | GM-CSF//D24 deletion in the E1A gene (inactivates pRB) | Replication in cells with a dysregulated retinoblastoma pathway | I | Pembrolizumab, cyclophosphamide | NCT03003676 |
| GEN0101 (HVJ-E; TSD-0014) b | Hemagglutinating virus of Japan (HVJ) | RNA fragmentation by UV irradiation (inactivation); envelope presents fusion activity | Apoptosis and type-1 IFN response mediated by retinoic acid-inducible gene-I (RIG-I) activation in tumor cells upon viral RNA recognition | I/IIa | — | Kiyohara et al. (2020) |
| Ib/II | Pembrolizumab | NCT03818893 |
a
by the U.S. FDA, Food and Drug Administration.
b
Non-replicating vector.
EGFR, epidermal growth factor receptor; GM-CSF, Granulocyte Macrophage Colony-Stimulating Factor; IFN, interferon; IL2, Interleukin 2; TNF-α, tumor necrosis factor alpha.