Figure 7. Effect of systemic F-araAMP plus Ad/TvPNP or Ad/EcPNP on D54 tumor growth.

Parental D54 tumor cells (no PNP expression) were established subcutaneously on flanks of nude mice. Thirteen days following implantation, tumors were injected with 2 × 10¹¹ virus particles of Ad/EcPNP (squares) or Ad/TvPNP (diamonds) once a day for 3 consecutive days (i.e., days 13, 14, and 15). Each administration of adenoviral vector was in a 150 μl volume by 8 separate injections of approximately 20 μl each in an effort to evenly distribute transgene expression throughout tumor tissue. On day 18, adenovirus treated mice were given 120 mg/kg F-araAMP (dissolved in saline) IP (0.2 ml/10 g of body weight) three times per day (every 4 hours) on days 18, 19, and 20) (filled squares and diamonds) or vehicle (open squares and diamonds). Tumors in the no-treatment group (open circles) were injected with 150 μl saline intratumorally once a day for 3 days (13, 14, 15), and subsequently injected IP (0.2 ml/10 g of body weight) with saline three times a day for 3 consecutive days (18, 19, 20). The rates of cleavage of MeP-dR and F-araA in Ad/TvPNP treated tumors on day 18 were 2,900 ± 600 units and 130 ± 40 units, respectively; in tumors treated with Ad/EcPNP, rates of cleavage were 3,100 ± 1,500 units and 26 ± 10 units, respectively (N=3). Each treatment arm contained 8 mice. Five percent weight loss was noted in mice treated with Ad/EcPNP plus F-araAMP, with 13% weight loss in mice treated with Ad/TvPNP plus F-araAMP, which resolved. One mouse died in the Ad/TvPNP plus F-araAMP treatment group, which could be attributable to F-araAMP or combination treatment. No weight loss or deaths were noted in other treatment groups. Growth rates of tumors treated with F-araAMP plus Ad/EcPNP or Ad/TvPNP were significantly different than vehicle treated controls (P< 0.001).