Recombinant DNA Advisory Committee - 10/7-8/91 
was performed where transduced irradiated PA-1 cells were put into an animal. The 
only valuable information obtained from this experiment was the survival time of the 
mice. 
Dr. Walters said the HGTS had provisionally approved the protocol with the stipulation 
that: (1) experiments be performed to ensure that the retrovirus is not producing any 
helper virus; and (2) the cell lines should be assayed for sterility. Dr. Wivel said there 
was a detailed discussion at that meeting about the particular cell line chosen. There 
was concern that PA-1 is a high-passage line that may carry mycoplasma. 
Dr. Freeman responded that he plans to use Stage I, II, and III ovarian cancer patients 
who have been previously treated and have evidence of residual disease. These patients 
will be treated with irradiated gene-modified tumor cells that contain the TK gene. 
Patients will then receive three repeated doses of ganciclovir. The goal here is to 
evaluate safety and side effects, to determine a maximum cell dose, to evaluate the 
immunologic response, and to observe any clinical effects. 
Dr. Freeman described the suggestions made at the HGTS meeting that he had since 
incorporated into the protocol. Dr. Leventhal had suggested that a laparoscopy should 
be performed before and after therapy in order to determine the extent of tumor burden. 
Dr. Parkman suggested that they thoroughly and carefully follow the immune status of 
these patients by their response to skin testing. The consent form has been revised. 
Dr. Freeman said that the patients involved will have been initially diagnosed as Stage I, 
II, or III. Stage I patients may have as much as a 60% chance of long-term survival. If 
they relapse after having completed surgery and chemotherapy, there is no known 
treatment to prolong their survival. It is a prerequisite of the study that these patients 
have received conventional chemotherapy treatment with Cisplatin or Carboplatin since 
these are proven effective in the treatment of ovarian cancer. Therefore, patients must 
have been treated with the most effective drug prior to acceptance into this protocol. 
He noted that Stage IV patients will not be used. Stage I, II, and in patients have 
disease confined to their peritoneal cavity, whereas Stage IV represents patients with 
metastatic disease. The population of patients chosen will not have large tumor masses, 
so they are not end-stage patients. Often the patient has disease detectable only by 
elevated levels of a serum marker. 
Dr. Freeman described the mechanism of action of ganciclovir and the HSV-TK gene. 
Ganciclovir must be phosphorylated to be effective. Once phosphorylated, it cannot 
cross cell membranes, therefore, this compound cannot be injected directly into the 
patient. The vector to be used, STK, has an LTR promoted neomycin gene and a SV40 
promoted thymidine kinase gene. It is hypothesized that putting this vector into tumor 
cells will make them susceptible to killing by ganciclovir. 
Recombinant DNA Research, Volume 15 
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