In subsequent series of experiments, we have evaluated the GITKSVNa vector in 
the 9L brain tumor model and the various in vitro studies previously done with the 
GINsCTK vector, using both producer and non-producer cells. Although no difference 
was found in our results between the different vectors (STK, GINsCTK, GITKSVNa), 
we believe that the GITKSVNa vector is a better choice for use in a human clinical trial 
since it has an improved titer (5x1 0^ versus 1 xl 0 4 ) and has further safety 
modifications to prevent the development of replication-competent virus compared to 
the other available vectors. 
F. Bystander Effect. 
One of the unique features of the tumor rejection in the HS-tk system in 
mice is the observation that not all the tumor’s cells must contain the inserted gene in 
order to be killed upon ganciclovir challenge. In mice given a subcutaneous tumor in 
which 100% of the cells carry the HS-tk gene, complete tumor regressions are seen 
following GCV treatment. Interestingly, when tumors established from cell mixtures 
containing 50% HS-tk gene-modified cells mixed with 50% wild-type unmodified tumor 
cells were treated with GCV, almost all tumors (14/15) regressed. Even in situations 
where the mixed tumor contained 90% unmodified, wild-type tumor cells mixed with 
only 10% HS-tk modified tumor cells, complete regression of the cancer was observed 
with GCV treatment in 9 of 15 animals (see Table below). 
The effect of GCV on the incidence of tumor growth in mice injected with mixtures of various 
proportions of HS-tk gene-transduced and wild type tumor cells. 
Tumor Mixture Recioient 
Incidence of 
Paloable Tumors 
% wild type 
% HS-tk tumor 
2 weeks 
5 weeks 
0 % 
100% 
0/15 
2/15 
50% 
50% 
0/15 
1/15 
90% 
10% 
3/15 
6/15 
1 00% 
0% 
12/15 
15/15 
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Recombinant DNA Research, Volume 15 
