Table 2.
List of IL-12 expressing oncolytic viruses (other than OHSVs) and their efficacy in pre-clinical cancer models.
| Virus | Strain | Cancer Model | RoA | Dose | Efficacy | Ref |
|---|---|---|---|---|---|---|
| Adenovirus | Ad5-yCD/ mutTKSR39 rep-mIL12 |
Subcutaneous TRAMP (C2 prostate adenocarcinoma) | I.T. | 5 × 108 pfu | Improved local and metastatic tumor control. Increased NK and CTL cytolytic activities. Significantly increased survival, levels of IL-12 and IFN-ƴ in serum and tumor. |
[42,43] |
| Ad-TD-IL-12, Ad-TD-nsIL-12 | Subcutaneous HPD1NR (pancreatic cancer) | I.T. | 1 × 109 pfu | 100% tumor eradication and survival of both IL-12 modified Adenovirus treated animals. Ad-TD-IL-12, but not Ad-TD-nsIL-12 resulted in a significant increase in CD3+CD4−CD8+ populations in the spleen. Level of splenic IFN-γ, IP-10 and lymph node IFN-γ were lower in Ad-TD-nsIL-12 compared to Ad-TD-IL-12 treated hamster. |
[44] | |
| Ad-ΔB7/IL12/GMCSF | Subcutaneous B16-F10 (melanoma) | I.T. | 5 × 107 pfu | Primary tumor growth was better controlled in Ad-ΔB7/IL12/GMCSF and Ad-ΔB7/IL12 compared to Ad-ΔB7GMCSF or PBS. Increased tumor infiltrating CD86+ APCs and enhanced CD4+ and CD8+ T cell-mediated Th1 antitumor immune response.Reduced VEGF expression in the tumor treated with oncolytic Ad co-expressing IL-12 and GM-CSF or IL-12 alone. IFN-γ, TNF-α and IL-6 were higher in Ad-ΔB7/IL12/GMCSF and Ad-ΔB7/IL12 compared to Ad-ΔB7GMCSF or PBS. |
[45] | |
| RdB/IL-12/ IL-18 |
Subcutaneous B16-F10 (melanoma) | I.T. | 1 × 108 pfu | 95% and 99% tumor growth inhibition was observed in treatment with RdB/IL-12 and RdB/IL-12/IL-18, respectively. Increased Th1/Th2 cytokine ratio and increased tumor infiltration of CD4+ T, CD8+ T and NK cells. Promoted differentiation of T cells expressing IL-12Rβ2 or IL-18Rα. |
[46] | |
| RdB/IL12/ DCN |
Orthotopic 4T1 (Triple negative breast cancer) | I.T. | 2 × 1010 VP | Both of the IL-12-expressing oncolytic Ads showed similar tumor growth inhibition up to day 9 after initial treatment. RdB/IL12/DCN increased upregulation of IFN-γ, TNF-α, infiltrating cytotoxic lymphocytes, downregulation of TGF-β expression and T-regs compared to RdB/IL12 and RdB/DCN. |
[47] | |
| YKL-IL12/B7 | Subcutaneous B16-F10 (melanoma) | I.T. | 5 × 108 pfu | Tumor growth was suppressed in both YKL-IL12 and YKL-IL12/B7 treated mice vs PBS. YKL-IL12- or YKL-IL12/B7-treated mice produced a significantly greater level of IFN-γ, infiltrating APCs, CD4+, CD8+ compared with PBS. |
[48] | |
| Ad-ΔB7/ IL-12/4-1BBL |
Subcutaneous B16-F10 (melanoma) | I.T. | 5 × 109 VP | 100% of mice in the Ad-ΔB7/IL-12/4-1BBL group survived >30 days after initial viral injection compared with 20% of that in virus expressing either IL-12 or 4-1BBL. Mice treated with Ad-ΔB7/IL-12 or Ad-ΔB7/IL-12/4-1BBL had greater amount of tumor infiltrating CD4+ and CD8+ compared to Ad-ΔB7/4-1BBL and Ad-ΔB7. |
[49] | |
| Measles virus | MeVac FmIL-12 | Subcutaneous MC38ce (colon carcinoma) | I.T. | 5 × 105–1× 106 ciu | Tumor remissions in 90% of animals. Driven polarization of Th1-associated immune response and increased tumor infiltrating CD8+ T cells. Increased IFN-γ and TNF-α, and polarization of Th1-associated immune response. Co-expression of IL-12 and IL-15 showed synergistic effect. |
[20,50] |
| Maraba Virus | MG1-IL12- ICV |
CT26 and B16F10 peritoneal carcinomatosis | I.P | Seeding dose 5 × 105, then 1 × 104 on day 3 | Reduced tumor burden and improved mouse survival. Activated and matured DCs to secrete IP-10, and activated and recruited NK cells. Increased production of IFN-γ |
[51] |
| Newcastle disease virus | rClone30– IL-12 |
Orthotopic H22 (hepatocarcinoma) | I.T. | 1 × 107 pfu | Reduced tumor volume and improved percentage of survival. Increased IFN-γ and IP-10. Co-expression of IL-12 and IL-2 showed synergistic effect. |
[52] |
| Semliki Forest virus | rSFV/IL12 | Subcutaneous B16 (melanoma) | I.T. | 107 IU | Single injection with SFV-IL12 resulted in significant tumor regression. 2 days after injection, IFN-γ production increased with inhibition of tumor vascularization. Splenic IP-10 and MIG expression was increased. |
[53] |
| SFV/IL12 | Subcutaneous P815 (mastocytoma) | I.T. | 106 IU | Significantly delayed P815 tumor growth. 40–53% of mice exhibited complete tumor regressions. Induced high levels of IFN-γ production in draining lymph nodes. |
[54] | |
| SFV/IL12 | Subcutaneous MC38 (colon adenocarcinoma) | I.T. | 108 particles | Reduced tumor volume and improved percentage of survival. Increased tumor-specific CD8+ T lymphocytes. Enhanced the expression of CD11c, CD8α, CD40, and CD86 of tumor-infiltrating M-MDSCs in the presence of an intact endogenous IFN-I system. |
[55] | |
| SFV-VLP- |
Syngeneic RG2 (rat glioma) | I.T. | 5 × 107 (low-dose) or 5 × 108 (high-dose) | Reduction in tumor volume (70%—low dose; 87%—high dose) | [56] | |
| Vesicular stomatitis virus (VSV) | VSV-IL12 | Orthotopic SCC VII (squamous cell Carcinoma) | I.T. | MOI 0.01 | Significant reduction in tumor volume, and prolonged survival. | [57] |
| Sindbis virus | Sin/IL12 | Orthotopic ES-2 cells (ovarian clear cell Carcinoma) | I.P | 107 pfu | Reduced tumor growth and improved survival. Activated and matured DCs, activated and recruited NK cells. Increased production of IFN-γ. |
[58] |
∆—deletion, RoA—Route of administration, I.T—intratumorally, IP—intraperitoneally, pfu—plaque forming unit, ref. —reference, MOI—multiplicity of infection, VP—viral particle, IU—infectious units.