Recombinant DNA Advisory Committee - 10/7-8/91 
contact with all the TK- cells. Using this model, he accomplished that experiment. TK- 
cells were administered to the mice at day zero followed by the administration of TK+ 
cells and ganciclovir at a later time. Prolonged survival was observed. 
Dr. Kelley said that as the animal experiments become more and more relevant to the 
human proposal, the ratio experiments become increasingly critical and should be 
presented to the RAC. 
Dr. Leventhal said it would be helpful to have median survival depicted on all of the 
graphs to give an indication of how close to death these animals were when treatment 
commenced. She said that there was not enough information on the slides which made 
them extremely difficult to follow. 
Dr. Freeman restated that he had three animal models: (1) The subcutaneous injection 
of the cells followed by treatment with ganciclovir. (2) The mixture of the TK+ and TK- 
cells prior to subcutaneous injection of the mixture on day zero and subsequent 
challenge intraperitoneally on day five with TK+ cells. In this experiment, the animal 
survival was prolonged. (3) The subcutaneous injection of TK- cells on day zero, and 
subcutaneous injection of TK+ cells on day one or day five. Dr. Kelley asked if there 
are visible tumor masses by day five, when the TK+ cells are administered. Dr. 
Freeman replied there were no visible tumor masses. Mr. Capron asked if he had 
control mice to look at the tumors at day five in the absence of the second TK+ cell 
injection. Dr. Kelley said the tumors were not visible at day five. Mr. Capron asked if 
autopsies are performed on the mice. Dr. Freeman replied he had not autopsied the 
mice at five days. 
Dr. Freeman said that with the two mechanisms combined, the system will be more 
effective and lead to the elimination of a major portion of the intraperitoneal tumor. 
Perhaps the effect of the TK+ cells on the TK- cells along with the subsequent immune 
response may actually eliminate metastatic disease. He said he has established three 
separate in vivo animal models, as well as in vitro performed experiments, that indicate 
10-50% of TK+ cells may lead to the elimination of nearby unmodified tumor cells and 
prolong survival of the animals. 
Dr. Kelley said as the experiments have become increasingly relevant to the proposed 
human experiment, the precise ratio of TK+ to TK- cells has to be determined. 
Dr. Freeman introduced his colleague, Dr. Craig McCune, to comment on animal 
models. 
Dr. McCune said he is a medical oncologist who began to work with Dr. Freeman in the 
creation of the proposed clinical study. He acknowledged that the question of when to 
Recombinant DNA Research, Volume 15 
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