Human Gene Therapy Subcommittee - 11/21-22/91 
ganciclovir. What is the estimated frequency of these mutations? Dr. Overell responded 
that the CMV system is a heterogeneous virus population in which 99.9% of the virus 
particles confer both hygromycin and ganciclovir sensitivity. Therefore, in 10 transduced 
T cell clones, there will probably be no resistant clones. Dr. Mclvor stated that the 
frequency of mutation should be on the order of 1 in 10 6 cells. Dr. Greenberg noted 
that even if some of the cells are resistant and therefore non-ablatable, there should be 
no risk to the patient from the few remaining cells. 
Dr. Mclvor inquired about the transduction frequency in these T cell clones. What 
about multiplicity of infection? Dr. Greenberg answered that the multiplicity of infection 
is approximately a 1:1 ratio, and that he and his colleagues have been successful in 
transducing every T cell clone that has been attempted. 
Ms. Meyers asked if the drug Foscamet could be used as an alternative therapy for CMV 
infection. Dr. Greenberg said that ganciclovir has been proven to be the most effective 
treatment; therefore, it is the choice of treatment for the infection. In addition, the FDA 
has not approved the use of Foscamet in the bone marrow transplant setting because of 
the toxic effects that have been observed when the drug is administered in combination 
with cyclosporin. 
Dr. Leventhal commended the investigators for including a stopping rule that considers 
failure as well as success. In the event that the therapy is working well, the protocol will 
be stopped early. However, she suggested that a section be included in the informed 
consent regarding permission for postmortem. She stated that she was in favor of 
approving the protocol. 
Subcommittee Motion 
A motion was made by Dr. Epstein and seconded by Dr. Mclvor to recommend the 
protocol to the RAC. The motion passed by a vote of 11 in favor, 0 opposed, and 3 
abstentions. The HGTS suggested that the following changes should be incorporated 
into the informed consent document: (1) the following sentence should be added: 
"Because the gene modification procedure is relatively new, it is possible that despite our 
extensive efforts it may cause some unforeseen problems or even have the very remote 
possibility of causing death," and (2) a statement will be included informing the patient 
that they will not be responsible for the cost of generating the T cell clones; however, in 
the event of untoward consequences following the cell transfer, there would be costs 
associated with clinical care. 
Ms. Meyers asked if illness resulting from progression of the patient's disease could be 
distinguished from untoward effects resulting from the T cell therapy, would the patient 
be responsible for costs resulting from the negative effects of the therapy. Dr. 
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