Table 2.
oHSVs targeting GSCs. Genome structure, activity, and GSC models.
| Name | Genetic alterations | GSC Ref | In vivo model | Main results | Ref |
|---|---|---|---|---|---|
| RAMBO | -γ34.5Δ -Armed with Vasculostatin (Vstat120), under IE4/5pro |
(Wakimoto et al., 2012) | MGG23 implanted in immuno-deficient mice | -RAMBO extended median survival. -Vstat120 synergized with bevacuzumab and reduced migration and invasion. |
(Tomita et al., 2019) |
| VAE | -γ34.5Δ, ICP6-, -Armed with endostatin-angiostatin fusion |
(Zhang et al., 2014) | GBM-SC implanted in nude micee | -VAE extended median survival over parental virus or recombinant endtostatin. -Decreased microvessel density. |
(Zhang et al., 2014) |
| MG18L | ICP6-, LacZ+, Us3Δ | (Wakimoto et al., 2009; Wakimoto et al., 2012) | BT74, MGG4 or MGG31 implanted in athymic mice | -PI3K/Akt inhibitor + MG18L kills GSCs not astrocytes. -PI3K/Akt inhibitor + MG18L prolongs survival to 50% cures. -Combination of PARPi + MG18L kills PARPi-sensitive and -resistant GSCs in vitro and extends median survival. -Combination of TGF-β inhibitors + MG18L increase recurrent GSC killing. -TGF-β inhibitors + MG18L result in 60% cured mice. |
(Kanai et al., 2011; Esaki et al., 2017; Ning et al., 2017) |
| Δ68H-6 | γ34.5 BBD deleted, ICP6−, LacZ+ | (Wakimoto et al., 2009) | MGG4 implanted in athymic mice | -Δ68H-6 increased survival. -Δ68H-6 is safe. |
(Kanai et al., 2012b) |
| NG34 | -γ34.5Δ, ICP6−. -hGADD34 driven by the nestin enhancer-hsp68pro |
(Nakashima et al., 2018) | G35 implanted in athymic mice | -more cytotoxic in hGSCs than rQNestin34.5, but less neurotoxic. -extended survival of hGSC-bearing mice. |
(Nakashima et al., 2018) |
| G47Δ-mIL12 | -γ34.5Δ, ICP6−, ICP47Δ, LacZ+. -Armed with mIL12 under HCMVpro. |
(Cheema et al., 2013) | 005 implanted in C57/BL6 mice | -antiangiogenic activity in vitro and in vivo. -Extends survival of mice with 005 tumors, dependent on T cells. |
(Cheema et al., 2013) |
| G47Δ-mAngio | -γ34.5Δ, ICP6−, LacZ+, ICP47/Us11proΔ, -Armed with murine angiostatin (mAngio) |
(Wakimoto et al., 2009) | MGG4 implanted in athymic mice | -G47Δ-mAngio prolonged mouse survival. -G47Δ-mAngio combined with G47Δ-mIL12 increased survival, virus spread, and decreased macrophages. |
(Zhang et al., 2013) |
| OV-Cmab-CCL5 | -γ34.5Δ, ICP6−,GFP+
-Armed with Cetuximab-CCL5 fusion protein under IE4/5pro. |
(Uchida et al., 2013) | GBM30-FFL implanted in NSG mice | -Multi-mechanistic efficacy in immuno-deficient and -competent -Increased migration of NK, macrophages, CD4+ and CD8+T cells. -OV-Cmab-CCL5 improves median survival 2.4-fold. |
(Tian et al., 2022) |
| OV-αCD47-G1 | -γ34.5Δ, ICP6−, GFP+
-Armed with αCD47-IgG1 under IE4/5pro. |
(Xu et al., 2021) | GBM43 implanted in athymic mice | OV-αCD47-G1 treatment in vivo releases αCD47 into the TME and prolongs survival. | (Xu et al., 2021) |
| OV-IL15C | -γ34.5Δ, ICP6−, GFP+ -Armed with hIL15-IL15Rα sushi domain under IE4/5pro. |
(Uchida et al., 2013) | GBM30 implanted into NSG mice | -hGSC killing by NK cells treated with conditioned media. -extended survival with hCD8+ T cells and with EGFR-CAR NK. |
(Ma et al., 2021) |
| oHSV-TRAIL | -γ34.5Δ, ICP6−, LacZ+, ICP47/Us11proΔ -Armed with TRAIL under IE4/5pro. |
(Wakimoto et al., 2012; Esaki et al., 2017) | MGG23 and MGG31 implanted in athymic mice | oHSV-TRAIL increased survival in mice with TMZ-resistant primary and recurrent GSCs | (Jahan et al., 2017) |
| OV-CDH1 | -γ34.5Δ, ICP6−, GFP+
-Armed with e-cadherin (CDH1) under IE4/5pro. |
(Uchida et al., 2013) | GBM30 implanted in athymic mice | OV-CDH1 mediated enhanced viral spread and increased NK infiltration. | (Xu et al., 2018) |
| KNE | -gB:NT, scFv EGFR-retargeted gD Δ224-38. | (Uchida et al., 2013) | GBM30 implanted in athymic mice | -Antitumor efficacy in vivo, >50% long-term survivors. -safe in the brain of nude mice. |
(Uchida et al., 2013) |
| KGE4:T124 | -γ34.5Δ, ICP6−
-4x miR-124 target sequence in 3’UTR of ICP4 -EGFR-retargeted gD. |
(Uchida et al., 2013) | GBM30 implanted in BALB/c athymic mice | miR-124T sites in ICP4 gene did not affect antitumor efficacy | (Mazzacurati et al., 2015) |
| R-LM113 | -scFv HER2-retarged gD -wild-type backbone |
(Calzolari et al., 2008) | -mGBM-HER2 implanted in C57/BL6 mice. -BALB/c-HGG-HER2 in BALB/c mice. |
Antitumor efficacy in immunocompetent mouse models. | (Gambini et al., 2012; Reisoli et al., 2012) |
| R-613 | -scFv EGFRvIII-retargeted gD Δ6-38 -wild-type backbone. |
(Mazzoleni et al., 2010) | L0306 implanted in NOD/SCID mice | -R-613 infects EGFRvIII+ GSCs and spreads in vitro and in vivo. -Early, but not late treatments increase mice survival. |
(Appolloni et al., 2021) |
| R-115 | -scFv HER2-retarged gD. -wild-type backbone. -Armed with mIL12 under HCMVpro. |
(Calzolari et al., 2008) | -mHGGpdgf-hHER2 implanted in C57/BL6 mice. | -Significant improvement of overall median survival, but not different than R-LM113. -30% of mice cured. |
(Alessandrini et al., 2019) |
| oHSV/Nb-gD | -γ34.5Δ, ICP6−, GFP+, ICP47Δ. -Nanobody-hCXCR4 retargeted gD. |
(Sanchez Gil et al., 2022) | T033 implanted in athymic mice | -Infected CXCR4-expressing GSCs. -Treatment of mice with T033 tumors did not extend survival. |
(Sanchez Gil et al., 2022) |
BBD, Beclin-1 binding domain; CM, conditioned media; MMP9, Matrix Metalloproteinase 9; N/A, not applicable; NSG, NOD/SCID/IL2rg; PARPi, Poly-ADP-ribose polymerase inhibitor; ULBP3, UL16 binding protein 3; VEGF, vascular endothelial growth factor.