Table 1.
List of OHSV-IL12s and their efficacy in pre-clinical cancer models.
| Virus | Genomic Modification | Cancer Model | RoA | Dose (pfu) | Efficacy | Ref. |
|---|---|---|---|---|---|---|
| G47Δ-mIL12 | ΔICP6, Δ∆ICP34.5, ΔICP47, ◦LacZ, ◦mIL-12 | Intracranial 005 GSC (Glioblastoma) | I.T. | 5 × 105 | Inhibited intracranial tumor growth and extended survival. Promoted IL-12 expression, stimulated IFN-γ production, upregulated IP-10, and inhibited VEGF. Polarized TH1 response and inhibited T-regs function. |
[19,30] |
| T-mfIL12 | ΔICP6, Δ∆ICP34.5, ΔICP47, ◦mIL-12 | Intracerebral Neuro2a (neuroblastma) | I.V. | 5 × 106 | Prolonged survival (Mock vs. T-mfIL12, p < 0.05), although not statistically significant versus T-01 treatments. | [31] |
| NV1042 | ΔICP0, ΔICP4, ΔICP34.5, ΔUL56, ΔICP47, Us11Δ, Us10Δ, UL56 (duplicated), ◦mIL-12 | Subcutaneous SCC VII (Squamous Cell Carcinoma) | I.T. | 1 × 107 | Reduced tumor volume and improved survival (3 doses of 2 × 107 pfu). 57% of mice from NV1042 group rejected subsequent SCC re-challenge in the contralateral flank compared with 14% in NV1023 or NV1034 group. |
[32] |
| I.V. | 5 × 107 | NV1042 treatment resulted in 100% survival, in contrast to 70% of NV1023 and 0% of PBS. | [33] | |||
| M002 | ∆ΔICP34.5, ◦mIL-12 | Intracranial X21415 (Pediatric embryonal tumor); D456 (pediatric glioblastoma); GBM-12 and UAB106 (adult glioblastoma) | I.T. | 1 × 107 | M002 significantly prolonged survival in mice bearing all 4 types of tumor compared to saline. No difference in survival was observed compared with G207, excluding X21415 with high levels of nectin-1 | [34] |
| Intracranial SCK (brain metastasized breast cancer) | I.T. | 1.5 × 107 | Single injection of M002 extended the survival of treated animals more effectively than a non-cytokine control virus. | [35] | ||
| Xenograft SK-N-AS and SK-N-BE (2) (human neuroblastoma); subcutaneous Neuro-2a (murine neuroblastoma) |
I.T. | 1 × 107 | Significant decrease in tumor growth were observed in both SK-N-AS and SK-N-BE (2) cell lines. Extended median survival compared to the parent R3659. | [36] | ||
| HuH6 (human hepatoblastoma; G401 (human malignant rhabdoid kidney tumor); SK-NEP-1 (renal Ewing sarcoma) | I.T. | 1 × 107 | M002 significantly reduced tumor volume and increased survival over those treated with vehicle alone in all three different xenograft models. | [37] | ||
| R-115 | Virulent with retargeted HER-2, ◦mIL-12 | pLV-HER2- nectin-puro |
I.P. | 1 × 108 to 2 × 109 | Induced greater local and systemic anti-tumor immunity and durable response than unarmed R-LM113 in both early and late schedule. All mice that survived from primary tumor challenge were protected from the distant challenge tumor and subsequent re-challenge. Increased number of CD8+ and CD141+ cells, PD-L1+ tumor cells, and Treg with a decrease in the number of CD11b+ cells. Enhanced Th1 polarization and increased expression of IFN-γ, IL-2, Granzyme B, T-bet and TNFα and tumor infiltrating lymphocytes |
[38] |
| Orthotopic mHGGpdgf- hHER2 (glioblastoma) |
I.T. | Low dose: 2 × 106
High dose: 1 × 108 |
27% of mice treated with R-115 (n = 6, 4 low-dose arm and 2 high-dose arm) alive 100 days after the virus treatment versus all mice died within 48 days. Increased infiltrating CD4+ and CD8+, and expression of IFN-γ | [39] | ||
| vHSV-IL-12 | ΔICP6, Δ∆ICP34.5, ◦mIL-12 | Subcutaneous Neuro2a (neuroblastoma) | I.T. | 1 × 104 | Significantly reduced tumor growth versus vHSV-null and other cytokine armed groups. | [40] |
| T2850 | ∆IR 15,091bp, ◦mIL-12 | Subcutaneous A20 (Murine B Lymphoma), MC38 (colon adenocarcinoma), MFC (Murine Forestomach Carcinoma) | I.T. | 1 × 107 | Reduced tumor volume compared to IL-12 unarmed parental group. IFN-γ level was markedly increased in the tumor bed and sera of mice infected with both T2850 and T3855 by day 4. | [41] |
| T3855 | ∆IR 15,091bp, ◦mIL-12, ◦mPD-1 | Subcutaneous B16 (melanoma) | 5 × 106, 1 × 107, 3 × 107 | |||
| T3011 | ∆IR15,091bp, ◦hIL-12, ◦hPD-1 | Subcutaneous B16 (melanoma) | I.T. | 5 × 106, 1 × 107 or 3 × 107 | Reduced tumor volume as compared with control group. | [41] |
∆—deletion, ◦ insertion, RoA—Route of administration, I.T—intratumorally, IP—intraperitoneally, pfu—plaque forming unit, ref.—reference, VEGF—vascular endothelial growth factor.