Table 3.
List of Armed oHSVs for GBM Treatment
| Armed Transgene | oHSV | Strain | Genomic Modification | GBM Model | PFU (Doses) | Results and References |
|---|---|---|---|---|---|---|
| Cytokines | G47∆-mIL12 | F | ∆ICP6, -/-γ34.5, ∆ICP47, +LacZ, +mIL-12 | 005 GSC | 5×105 (2 doses) | G47∆-mIL12 significantly extended survival with 10% mice surviving long term compared to 0% in control virus (G47∆-Empty) group.33 |
| M002 | F | -/-γ34.5, +mIL-12 | Patient’s GBM tumors | 1×107 (1 dose) | - Pediatric GBM samples with high nectin-1 expression: M002 treatment led to tumor eradication in 8/10 animals compared to 3/10 animals in the G207 group.58 - Pediatric GBM samples with low nectin-1 expression and adult GBM samples: M002 treatment showed trend of improved median survival versus G207 treatment.58 |
|
| oHSV-Flt3-L | F | ∆ICP6, -/-γ34.5, ∆ICP47, +LacZ, +Flt3-L | CT-2A | 2x106 (1 dose) | Treatment with G47Δ-Flt3L led to 40% long-term survivors compared to 0% in G47Δ-Empty treatment.60 | |
| oHSV-TRAIL | F | ∆ICP6, -/-γ34.5, ∆ICP47, +LacZ, +TRAIL | LN229-FmC GBM | 2×108 (2 doses) | The median survival of mice treated with oHSV-TRAIL was 69 days, which was significantly longer than PBS group (50.5 days) or unarmed oHSV group (49 days).61 | |
| GSC23-FmC and GSC31 | GSC23-FmC - 2×106 (2 doses) and GSC31 2×106 (1 dose) | - GSC23-FmC: The median survival of mock group (44 days) was significantly lower than oHSV-TRAIL (55 days).62 - GSC31: oHSV-TRAIL significantly extended median survival (81 days) with 40% long-term survivors compared to 0% (median survival - 26 days) in the mock mock group.62 |
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| Angiogenic inhibitors | G47∆-mAngio | F | ∆ICP6, -/-γ34.5, ∆ICP47, +LacZ, +mAngio | U87 | 5×106 (2 doses) | - Subcutaneous U87 model: G47∆-mAngio delayed tumor growth by 4 days compared to G47∆-E.67 - Intracranial U87 model: Treatment with G47∆-mAngio resulted in 40% of mice surviving over 150 days and significantly prolonged animal survival compared to G47∆-E.67 |
| 1×106 (1 dose) | The median survival of G47Δ-mAngio was 66 days, which was significantly longer than G47Δ-Empty-treated group (53 days).57 | |||||
| MGG4 | 1×106 (1 dose) | The median survival of G47Δ-mAngio was 113 days, which was significantly longer than G47Δ-Empty group (98 days).57 | ||||
| VAE | F | ∆ICP6, -/-γ34.5, +endo-angio | Human stable GSC lines | Subcutaneous - 1×107 (1 dose) and intracranial 2x106 (1 dose) | Mice treated with VAE showed significant median survival extension compared with mice treated with control r-HSV (∆ICP6, -/-γ34.5) or Endostar.65 | |
| RAMBO | F | ∆ICP6, -/-γ34.5, +Vstat120 | U87ΔEGFR | 1×105 (1 dose) | The median survival of RAMBO was 28 days, which was statistically longer PBS-treated group (17 days).66 | |
| MGG23 | 1×105 (1 dose) | The median survival of RAMBO was 65 days, which was significantly longer than mice treated with PBS.66 | ||||
| U87ΔEGFR | 0.5×105 (1 dose) | The median survival of RAMBO was 29 days, which was statistically longer than 19 days in PBS-treated group.147 | ||||
| GADD34 | NG34 | F | ∆ICP6, -/-γ34.5, +GADD34 driven by nestin enhancer/promoter | U87ΔEGFR-RliFluc and G35 and GL261N4 | 2x105 (1 dose) | NG34 was shown to produce therapeutic efficacy as potent as rQnestin34.5 but with better tolerability.72 |
| Anti-PD-1 | NG34scFvPD-1 | F | ∆ICP6, -/-γ34.5, +GADD34 driven by nestin enhancer/promoter, +scFvPD-1 | GL261N4 | 1.5x106 (1 dose) | NG34scFvPD-1 treatment doubled the median survival time compared to non-anti-PD-1 expressing NG34 virus (69 vs 36.5 days).79 |
| CT-2A | 1.5x106 (1 dose) | Neither NG34scFvPD-1 nor NG34 led to a significant increase in median survival compared to mock group. However, 2/12 mice treated with NG34scFvPD-1 survived for 120 days.79 | ||||
| CDH-1 | OV-CDH1 | F | ∆ICP6, -/-γ34.5, +CDH-1 | GBM30, Gl261N4 and U87ΔEGFR | 2x105 (1 dose) | OV-CDH1 significantly prolonged median survival compared to unarmed OV-Q1 in all three models.84 |
| Chondroitinase ABC | OV-Chase | F | ∆ICP6, -/-γ34.5, +Chase | Gli36ΔEGFR–H2B-RFP and U87Δ EGFR | Subcutaneous −106 v.p. (6–7 doses), intracranical - 3x105 v.p. (1 dose) | In all models, treatment with OV-Chase significantly controlled tumor growth, resulted in extended survival compared to mock and unarmed oHSV.85 |
| OV-ChaseM | F | ∆ICP6, -/-γ34.5, +ChaseM | GBM30 | 3x105 v.p. (1 dose) | The median survival of OV-ChaseM treated group was 33 days versus 22 days in group receiving PBS.88 | |
| PTENα | HSV-P10 | F | ∆ICP6, -/-γ34.5, +PTENα, +eGFP | U87Δ EGFR | 1x105 (1 dose) | HSV-P10 significantly prolonged median survival, resulted in and 30% long-term survivors compared to 10% long-term survivors in unarmed HSVQ treatment group.92 |
| ULBP3 | oHSVULBP3 | F | ∆ICP4, +miR-124, +ULBP3 | XFM-Luc:PDGF,Cre | 1x106 (1 dose) | OHSVULBP3 inhibited tumor growth and prolonged median survival (18 days) compared to unarmed oHSV (8 days).95 |
| oHSVULBP3-MMP9 | F | ∆ICP4, +miR-124, +ULBP3, +MMP9 | XFM-Luc:PDGF,Cre | 1x106 (1 dose) | OHSVULBP3 showed statistically significant prolongation of median survival compared to OHSVULBP3-MMP9.96 | |
| ONCR-1 | F | ∆ICP4, -γ34.5, +miR-124, +ULBP3, +MMP9 | U251 | 3x105-3x106 (1 dose) | ONCR-1 inhibited tumor growth and prolonged survival compared to mock group.98 | |
| Pro-drug activating genes | MGH2 | F | ∆ICP6, -/-γ34.5, -UL39, +CYP2B1, +shiCE | Gli36ΔEGF | 1.4×106 | MGH2 did not prolong median survival compared to mock group.99 |
Abbreviations: PFU, plaque forming unit; (-), single deletion; (-/-), diploid deletion; ∆, mutation/inactivation; (+), insertion.