Recombinant DNA Advisory Committee - 10/7-8/91 
Dr. Gellert said he would like a clarification of the rationale of this therapy. There are 
two killing mechanisms discussed that are now merged together. They need to be 
discussed separately. If TK- cells are mixed with TK+ cells, in vitro , and treated with 
ganciclovir, both populations of cells are killed. However, this may be irrelevant because 
when the animal experiments were performed in immune-deficient mice, such as nude 
mice or irradiated mice, no killing of the TK- cells was observed. Therefore, in the 
mouse, it appears that the killing mechanism is related to an immune system response. 
The in vitro experiments may have no relevance. 
Dr. Gellert noted that the patients to be treated with the proposed therapy will have 
Stage I, II, or III cancer that have previously undergone treatment by surgery and/or 
chemotherapy, yet still have remaining tumor burden. He asked what the prospects of 
recovery for such patients might be if they were to receive chemotherapy of a different 
type. It is not made clear to the patient if they have other treatment options available. 
Dr. Gellert noted that the HGTS requested information on the structure of the 
transduction vectors. Information on only one of the vectors was submitted. At that 
HGTS meeting, there was a question raised about possible mycoplasma contamination of 
the PA-1 cell line that will be transduced. The investigator has not supplied the 
requested information; they say that the sterility tests are pending. If the vector 
information and the mycoplasma testing of the cell line are not available, consideration 
of the protocol should be postponed. 
Dr. Kelley noted that with regard to the expected likelihood of survival of the patients, 
the only patients to be treated should be those who have a relatively short life 
expectancy. He asked for a description of the imaging technique to be used in the 
measurement of pre-treatment tumor burden and called for an extensive discussion of 
the issues raised by the HGTS to ensure that they are resolved. 
Dr. Geiduschek expressed concern about various aspects of the protocol. He questioned 
the relevancy of the mouse model to the therapeutic scheme. He noted the cell dosages 
in the model experiments are very different from those proposed for the Phase I human 
study. The choice of the PA-1 human ovarian cancer cell line for transfer of the HSV- 
TK gene has been criticized on two counts: (1) the safety of the cell line is not yet 
assured; and (2) to the extent that the immune response to the patients' ovarian tumors 
are important to the functioning of the "vaccine." The use of heterologous cells is 
questionable. By opting for the technical advantage of using the established cell line, the 
project appears to risk uninformative outcomes in the Phase I study. The postulated 
therapeutic mechanism is still unclear. 
Dr. Geiduschek said the use of the term "cancer vaccine" in the informed consent 
document is problematic. Because the layperson assumes that vaccines work, the 
Recombinant DNA Research, Volume 15 
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