Recombinant DNA Advisory Committee - 06/1-2/92 
of ganciclovir. The timing was based on data derived from animal experiments. The 
optimal time for survival of these cells is approximately seven days in vivo. 
Dr. Hirano asked Dr. Oldfield if toxic effects were observed following the injection of 
the murine cells prior to surgical resection of the tumor? Will ganciclovir be 
administered to eliminate the producer cells? Dr. Oldfield stated that ganciclovir would 
be administered in the event that toxic effects were observed. Dr. Oldfield added that if 
there is no significant response to the initial treatment, a second injection of cells will 
not be administered. If patients exhibit unequivocal evidence of response to treatment, 
then more treatments would be considered. 
Regarding patient hypersensitivity to murine cells, Dr. Oldfield said that screening 
questions would be included so that patients could document past hypersensitivity 
responses to mice. Dr. Blaese noted that the majority of murine sensitivity is to dander 
or albumin, neither of which is present in this preparation. 
Dr. Parkman asked the investigators to address the following questions: (1) What is the 
mechanism by which the bystander phenomenon occurs? (2) To what degree is this 
phenomenon due to the presence of the herpes virus TK gene in the murine cells? and, 
(3) To what degree are the human tumor cells being transduced by this phenomenon? 
Presentation~Dr. Ram 
Dr. Ram addressed the questions regarding vector transmission. He showed photographs 
of the injection site taken five days post administration of the murine cells. Although a 
slight localized breakdown of the blood/brain barrier was observed, there was no 
evidence of edema, shift of midline, or bacteriological toxicity. A magnetic resonance 
imaging (MRI) scan taken seven days post administration of ganciclovir showed a dark 
area representing the murine cells that had been destroyed by ganciclovir treatment. 
Dr. Ram presented data which demonstrated that no proliferation or toxicity was 
observed in animals 90 days post injection of TK producing murine cells. These control 
animals did not receive ganciclovir treatment. 
Dr. Parkman asked Dr. Ram exactly what areas of the brain would be excluded as 
possible injection sites. Dr. Ram responded that cells would not be injected into 
posterior foci, cerebellum, or brain stem (including midbrain, medulla, and the spinal 
cord). 
Dr. Ram showed histological evidence in the monkey model that murine producer cells 
were completely destroyed three weeks following administration of ganciclovir. He 
hypothesized that the survival time of these producer cells following ganciclovir 
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