Table 2.
Examples of oHSV in preclinical immune competent models
| Tumor model | Virus/combination | Outcome | Reference |
|---|---|---|---|
| Glioblastoma (orthotopic) U87ΔEGFR (cell line) balb/c-nu/nu mice |
RAMBO HSVQ expressing VSTAT120 Cilengitide (integrin inhibitor) |
Combination 39.5 days (p < 0.005 vs control) RAMBO 29 days Cilengitide and control 19 days |
Fujii et al. (2013) |
| Glioblastoma (orthotopic) U87ΔEGFR (cell line) nu/nu mice |
RqNestin - HSVQexpressing ICPγ34.5 under control of nestin promoter | rQNestin 7/9 mice LTS ( > 90 days; p < 0.0005) HSVQ1 2/10 mice LTS Control 0 LTS (median = 20 days) |
Kambara et al. (2005) |
| Glioblastoma (orthotopic) GBM8/BT74 (patient-derived stem-like cells) nu/nu mice |
G47Δ Temozolomide O6benzylguanine |
G47D/GBM8 plus TMZ 4/8 LTS median survival = 228 days; G47Δ alone vs G47Δ + TMZ, hazard ratio of survival = 7.1; p = 0.003 |
Kanai et al. (2012) |
| Cervical cancer (SQ) C33a in SCID mice Me180 in nude mice |
G207 (ICP34.5 deleted, ICP6 insertion mutation) External beam radiotherapy (XRT) |
Control (n = 11) 0 survivors XRT (n = 9) 0 G207 (n = 12) 0 XRT + G207 (n = 12) 5 |
Blank et al. (2002) |
| Glioblastoma (orthotopic) U87MG nu/nu mice |
R3616 (inactivated γ34.5) Ionizing radiation |
Control 0/19 survivors Radiation 3/30 R3616 4/33 R3616 and radiation 22/33 |
Advani et al. (1998) |
| Cholangiocarcinoma (SQ) KMBC, YoMi, SK-ChA-1 cells nu/nu mice |
NV1023 (γ 34.5/UL24/UL56/US11/ICP47 deletions) External beam radiotherapy (XRT) |
Tumor volume reduction (%, compared with control) KMBC YoMi SK-ChA-1 NV1023 50.0 37.1 27.5 XRT 53.5 24.6 68.1 NV1023 + XRT 80.0 85.9 75.1 |
Jarnagin et al. (2006) |
| Prostate cancer LNCaP human cell line (SQ) TRAMP-C2 mouse cell line nu/nu |
G207 (ICP34.5 deleted, ICP6 insertion mutation) ionizing radiation |
There was no therapeutic benefit from combining radiation with G207 in either a human or a mouse tumor model system. | Jorgensen et al. (2001) |
| Glioblastoma (orthotopic) U87ΔEGFR (cell line) athymic rats |
hrR3 CPA CVF |
Combination of intra-arterial hrR3, CVF, and CPA significantly increased the survival of athymic rats harboring intracerebral human glioma xenografts compared with other treatments. | Ikeda et al. (2000) |
| Glioblastoma (orthotopic) U87 (cell line) nude mouse |
G207 (ICP34.5 deleted, ICP6 insertion mutation) TMZ |
Combination 100% survival at 90 days G207 46 days TMZ 48 days |
Aghi et al. (2006) |
| NSCLC (SQ) NCI-H460 (cell line) SCID mice |
HSV-1716 Mitomycin C |
Final mean burden of flank tumor (g) Control 1.406 ± 0.079 Combination 0.793 ± 0.047 (43.6% reduction) HSV-1716 1.127 ± 0.139 (19.8%) MMC 1.122 ± 0.070 (20.2%) |
Toyoizumi et al. (1999) |
| Ovarian cancer (SQ) HRA Nude mice |
HR522 (hrR3 derivative with syncytial phenotype) GCV |
Survival over 60 days Combination (n = 9) 71% HR522 (n = 9) 22% GCV (n = 7) 0% |
Nawa et al. (2003) |
| Melanoma (SQ) human MDA-MB-435S (435S) SCID mice |
MGH2 (ICP6/γ34.5 deletions, two prodrug-converting transgenes insertion) Paclitaxel-TRAIL (PT) |
HSV and HSV in combination with PT significantly delayed the tumor growth compared with vehicle (p < 0.001). PT before virus injection was the most effective. | Nagano et al. (2008) |
XRT, X-ray treatment; SQ, subcutaneous; NSCLC, non-small cell lung cancer; SCID, severe combined immunodeficient; TMZ, temozolomide; CPA, cyclophosphamide; CVF, cyclophosphamide, vinorelbine and 5-fluorouracil; LTS, long-term survivors; MMC, mitomycin C; GCV, ganciclovir; PT, paclitaxel/TRAIL.