Figure 8. Effect of intratumoral F-araAMP plus Ad/TvPNP or Ad/EcPNP on D54 tumor growth.

Parental D54 human glioma tumors were treated intratumorally with vehicle (open circles), Ad/EcPNP (open squares), Ad/TvPNP (open diamonds), F-araAMP (filled circles), Ad/EcPNP plus F-araAMP (filled squares), or Ad/TvPNP plus F-araAMP (filled diamonds). Adenoviral vectors (2 × 10¹¹ VP) were injected into the tumors twice a day (at 6-hour intervals) for 3 consecutive days starting on day 20 post implant. Eighteen mg F-araAMP dissolved in 0.15 ml DMSO was injected into tumors once per day for 3 consecutive days starting on day 25 post implant. F-araAMP (0.15 ml), adenoviral vectors (0.2 ml), or PBS/3% sucrose control (0.2 ml) were injected into D54 tumors using 8 separate injections of approximately equal volume in an effort to evenly distribute the administered agents. Cleavage rates of MeP-dR and F-araA (on day 25) by EcPNP in the D54 tumors treated with Ad/EcPNP were 1,200 ± 900 units and 5 ± 4 units, respectively. Cleavage of MeP-dR and F-araA (on day 25) by TvPNP in D54 tumors treated with Ad/TvPNP were 2,200 ± 700 units and 150 ± 50 units, respectively. Each treatment arm contained 8 mice. There were no deaths or significant weight loss in any of the treatment groups. The growth of tumors in mice treated with F-araAMP plus Ad/EcPNP or Ad/TvPNP was significantly different than vehicle treated controls (P< 0.001) and was also significantly different than in mice treated with F-araAMP alone (P = 0.037 and 0.011, respectively).