We next studied the time kinetics of cell kill of TK positive cells by ganciclovir. 
Using either 10 uM or 1 uM GCV, the approximate peak and trough levels achieved in 
vivo, respectively, kbalb-STK cells were exposed over varying time periods to these 
GCV concentrations. We demonstrated that exposure of kbalb-STK cells to 10 uM 
GCV for only three hours resulted in almost 100% killing of the cell population (figure 
9). 
200 -i 
% 
>*. 
O 100 - 
© 
1 
u 
§ 
1 
0 ■+ 
kbalb-STK ( 1 uM) 
kbalb-STK (10 uM) 
0 3 6 12 18 24 48 
Hours Exposed to GCV 
Initial observations described above demonstrated that some STK transduced cells 
were resistant to GCV therapy in vitro. It was surprising to find that an HSV-TK (TK) 
positive cell population could be eradicated in vivo even if enough cells were 
inoculated to assure adequate numbers of GCV resistant tumor cells to form a tumor. 
The ability to kill TK positive tumor cells in vivo was r.^xt addressed. The kbalb- 
STK and control LNL transduced kbalb cells (figure 10), 2 x 10®, as well as three other 
murine tumors (SA-1 (figure 11), MC 207, and MC 205) were inoculated 
subcutaneously into syngeneic mice. Mice were treated with ganciclovir (150 
mg/kg/dose x 5-10 doses) beginning on day 0 or day 5 relative to time of tumor 
inoculation. Some animals received kbalb-STK or kbalb-LNL cells without GCV 
therapy. Mice which received STK transduced tumor cells and GCV therapy rejected 
their tumors, while the control groups did not. 
10 
Recombinant DNA Research, Volume 15 
[581] 
