Recombinant DNA Advisory Committee - 2/10-11/92 
who develop evidence of CMV infection; this constitutes approximately one-third to one- 
half of these patients. If patients are treated with T-cell clones, then acquire a CMV 
infection, they will receive ganciclovir despite the fact that they are enrolled in this 
protocol. 
Patients who have received T-cell clones, in which no toxicity is observed, and who still 
require ganciclovir to treat CMV infection can be infused with T-cell clones that do not 
contain the ablatable gene. The ability to insert this gene does not impact on whether 
these patients receive ganciclovir for normal therapeutic purposes. Before a study begins, 
it will be predetermined that the TK gene can function as a suicide gene. 
Dr. Greenberg addressed the issue of whether patients can survive long enough to undergo 
this type of therapy. Soon after the BMT, the patients need to start treatment. If patients 
are treated prophylactically with CTL clones specific for CMV, it has to be a rapid 
process. Techniques have been developed that allow the rapid and efficient growth of T- 
cell clones. These clones are ready to infuse 35 days post-BMT. The intention is that the 
patient's BMT will not be delayed as a consequence of the initiation of the study. The T- 
cell therapy should not impact the time required from the time the patient is identified to 
the time of transplant. 
Discussion 
Dr. Greenberg addressed the role of the foreign gene, and whether the expression of the 
foreign gene in the T-cells would impact on their survival in vivo. Although the study 
cannot precisely assess this issue, it can determine whether the cells expressing these 
proteins survive. If the T-cell clones are rapidly ablated because of the expression of the 
proteins, then the investigators will ask whether alternative genes are superior to Hy or 
HSV-TK genes in achieving long-term in vivo survival. 
Dr. Greenberg addressed the issue of laboratory safety stating that all of the laboratory 
workers have extensive experience in handling cells obtained from HIV seropositive 
patients and employ universal precautions. With the nature of the procedure, cells 
containing HIV will be in the laboratory for only a short period of time. 
Dr. Greenberg addressed the informed consent issue and emphasized that a single 
comprehensive form is used at the center rather than having many separate forms. Also, 
patients participate in a formal conference where the family members and the physician 
discuss all procedures. 
Dr. Leventhal asked whether the vector being used would behave differently in a cell that 
was free of the AIDS virus and whether the vector could become suddenly competent 
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