Table 2.
Summary viral constructs for the treatment of glioblastoma and other malignant gliomas
| Viral Vector | Mechanism/Pathway Involved | Effect(s) on Tumor Cell |
|---|---|---|
| Adenovirus | ||
| REIC/Dkk-3 + cRGD | Activation caspase-9; reduced expression B-catenin | Decreased proliferation rate |
| Antisense MMP-9 | Downregulation of MMP-9 activity | Impaired tumor invasiveness |
| DNX-2401 + pembrolizumab | Increased epitope presentation to CD8+ Tcells | Induced antiglioma immune response |
| AAV8 and AAV9 +IFN-B | Increase in tumor-associated microglia | Improved tumor sensitivity to chemoradiation; improved median survival |
| dsAAV2 | Downregulation of TGF-B | Suppressed tumor growth; reduced tumor immunosuppressive effects |
| Herpes Virus | ||
| G47Δ | Deletion of the γ134.5and α47 genes and a disabling lacZ insertion within ICP6; Murine angiostatin insertion | Gain of function mutation leading to increased MHC class I expression in infected cells this resulting in enhanced viral replication |
| HSVtk + Flt3L | Release of HMGB1 | Phagocytosis of tumor; activation of immune response |
| HSV-M032 | Deletion in both copies of γ134.5 gene; Insertion of Human IL-12 | Selective glioma cell replication and expression of IL-12 in infected glioma cells resulting in enhanced immune response and tumor cell lysis |
| HSV-G207 | Deletion in both copies of γ134.5 gene and disabling lacZ insertion in UL39 | Selective glioma cell replication |
| HSV-C134 | Deletion in both copies of γ134.5 gene, expression of the HCMVTRS1 gene product | Selective and enhanced glioma cell replication |
| rQNestin34.5v.2 | Deletion in γ134.5 gene and UL39; ICP-34.5 under control of synthetic nestin promoter | Selective and enhanced glioma cell replication |
| Lentivirus | ||
| Sh-SirT1 | Downregulation SirT1 | Increased tumor sensitivity to radiotherapy |
| Sh-TLX | Downregulation TLX; expression of TET3 | Impaired tumor growth and tumorigenicity of stem cells |
| GAS1 + PTEN | Decreased AKT and ERK 1/2 expression | Impaired tumor growth |
| Paramoxyvirus | ||
| Measles (MV-CEA) | Attenuated strain modified to express the carcinoembryonic antigen gene | Designed to track viral gene expression in vivo via serum analysis to optimize dosing and administration schedule without resorting to histologic tissue analysis |
| Measles (MV-NIS) | Attenuated strain modified to express human thyroidal sodium iodide symporter (NIS) gene | NIS can act as a reporter gene that enables the non-invasive tracking of viral localization, spread, gene expression and replication over time. NIS may also be used as a therapeutic transgene by allowing intracellular uptake of isotopes, such as131 [I] (radiovirotherapy) |
| Picornavirus | ||
| Poliovirus (PVSRIPO) | Enhanced immune cell infiltration; reduction of TIM-3 expression | Promote immune response and tumor inflammation |
| Retrovirus | ||
| Toca 511 | Increased delivery of 5-FC to tumor | Increased tumor sensitivity to radiotherapy |