Fig. 2.

Retargeting of HAdV5^HVR7 increases tumor-specific gene delivery after intratumoral injection. a 1.5 × 10⁶ HAdV5^HVR7 particles were injected into subcutaneous EGFR⁺ A431 tumor xenografts in Rag1^-/- mice. Gene delivery was analyzed 48 hpi by luciferase activity, and the values obtained were normalized to total protein amount. The experiment was performed with randomized groups and blinded. Virus alone (free knob) showed significant transgene signal in all analyzed organs other than kidney. Gene delivery to the liver was reduced by blocking the fiber knob with the adapter (blocked knob). EGFR-specific retargeting adapter significantly increased tumor infection (retargeted knob). Background signals from control injections with PBS are indicated by dashed lines (mean, each symbol represents one organ, n = 2–3 mice per group. RLU, relative light units. One-way ANOVA of log-transformed data, *P < 0.05, **P < 0.01, ***P < 0.001). b, c The tumor-to-liver ratio was calculated for each individual mouse. The tumor-to-liver ratio was 50 for the unmodified virus and 7200 for virus retargeted to EGFR (b). In the case of HER2 xenografts, the values were 1200 and 24,600 for unmodified and HER2-retargeted virus, respectively (c). Sc, subcutaneous. Pooled data from repeated independent experiments were used for statistics, and individual experiments are indicated (mean, each symbol represents the ratio of an individual, two-sided, unpaired Welch’s t-test of log-transformed data, *P < 0.05, **P < 0.01)