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. 2015 Mar 18;2:15003. doi: 10.1038/mto.2015.3

Figure 4.

Figure 4

Virally expressed two therapeutic antibodies targeting the TME further improve virotherapy. (a) Enhanced therapeutic effects of GLV-1h444 in A549 tumor-bearing nude mice. Mice (n ≥ 7) were treated with virus alone, Avastin+Erbitux, PBS alone, or virus in combination with Avastin and Erbitux. A single dose of virus (2 × 106 pfu/mouse) was given i.v. when tumor volumes reached 450 mm3. Avastin and Erbitux were administered i.p. at doses of 5 mg/kg and 3 mg/kg, respectively, twice per week for 5 weeks, starting at 10 dpi. The arrows indicate the beginning and end of Avastin and Erbitux treatment. Statistical analysis was performed using one-way ANOVA (***P < 0.001, **P < 0.01, *P < 0.05). Stars indicate the comparison of the GLV-1h68 group with the GLV-1h444 group (black), the GLV-1h68+Avastin+Erbitux group (open), and the PBS+Avastin+Erbitux group (gray). (b) Enhanced therapeutic effects of GLV-1h446 compared with its parental viruses in A549 tumor-bearing nude mice. Mice (n ≥ 7) were i.v. injected with each VACV strain alone at a dose of 2 × 106 pfu/mouse when tumor volumes reached 450 mm3. Statistical analysis was performed using one-way ANOVA (***P < 0.001, **P < 0.01, *P < 0.05). Stars indicate the comparison of the GLV-1h68 group with the GLV-1h446 group (black). (c) Enhanced therapeutic effects of GLV-1h444 and GLV-1h446 compared with their parental viruses in DU145 tumor-bearing mice. Mice (n = 5) were injected i.v. with each VACV strain alone at a dose of 2 × 106 pfu/mouse when tumor volumes reached 450 mm3. Statistical analysis was performed using one-way ANOVA (***P < 0.001, **P < 0.01, *P < 0.05). Stars indicate the comparison of the GLV-1h68 group with the GLV-1h444 group (black) and with the GLV-1h446 group (open). (d–f) Detection of antibodies in mice sera and the change of tumor volumes in mice bearing A549 tumors after VACV treatment. Blood samples were collected retro-orbitally at 7, 21, and 35 dpi. The concentration of antibodies in mice sera was determined by ELISA with precoated FAP, EGFR, and VEGF plates. Tumors were measured with a digital caliper. Statistical analysis was performed with a two-tailed unpaired Student’s t-test (***P < 0.001).