Scientific Abstract 
Ovarian cancer accounts for approximately 12,000 deaths per year. Many patients 
who die of this . disease have tumor which is confined to the peritoneal cavity. These 
patients’ tumor cells are resistant to chemotherapy and radiation. New 
biotechnologies have emerged over the past several years which may provide a novel 
therapeutic modality for patients with ovarian cancer. We have designed a study that 
uses an allogeneic genetically modified tumor cell line to inhibit or eradicate 
preexisting in situ tumor cells. This will be accomplished by injecting the irradiated 
genetically modified tumor cells into the peritoneal cavity of patients with subsequent 
treatment with the drug ganciclovir. 
Preclinical studies have demonstrated the utility of this approach. We have 
demonstrated that tumor cells containing the herpes simplex thymidine kinsae gene 
(TK) can be killed with the drug ganciclovir (GCV). When TK positive and TK negative 
tumor cells are mixed in culture and exposed to ganciclovir, all cells can be eradicated 
even if as few as 10% of the population is TK positive. Thus TK positive cells have a 
killing effect on the TK negative cells. In vivo murine studies demonstrated similar 
results. We showed that a mixture of TK positive and TK negative tumor cells injected 
subcutaneously could be eradicated when the animals were treated with ganciclovir. 
This study was extended to a murine model in which mice had preexisting 
intraperitoneal tumor cells. We demonstrated that the injection of irradiated TK 
positive cells with subsequent ganciclovir therapy could prolong animal survival. We 
further demonstrated that the I.P. injection of irradiated TK positive human tumor cells 
into mice with a preexisting tumor resulted in cure of approximately 20% of the mice. 
We have designed a phase I study to begin to apply the above described preclinical 
studies to patients with ovarian cancer Our studies primary objective is to evaluate the 
safety and side effects of treatment of ovarian cancer patients with an allogeneic gene- 
modified cancer vaccine which is administered intraperitoneally and activated by 
ganciclovir. 
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Recombinant DNA Research, Volume 15 
