Recombinant DNA Advisory Committee - 09/9-10/93 
experiment. As to transduction efficiency of the retroviral vector, Dr. Wong-Staal said 
the initial transduction rate is only a few percent. However, after G418 selection, the 
ribozyme-transduced T cells are resistant to challenge by two HIV isolates. Dr. Parkman 
commented that other investigators have encountered some technical difficulties in 
performing G418 selection of transduced cells obtained from patient samples due to non- 
specific toxicity to lymphocytes, particularly, in the scaling up of this procedure to obtain 
large quantity of cells for patient use. Dr. Wong-Staal agreed that a rehearsal of this 
isolation procedure at the clinical scale will be performed. Dr. Poeschla addressed 
questions on the assays that will be performed to detect HTV in the transduced 
lymphocyte preparations that will be administered to patients. Any preparation positive 
in the p24 HTV test will be discarded. 
Dr. Poeschla explained that there are differing opinions between the investigators and 
their IRB regarding the mandatory requirement for AZT administration. Not only is 
there controversy about the use of AZT, but the IRB has mistakenly assumed that AZT 
is useful for inhibiting murine RCR in the event of RCR contamination (AZT was used 
in Dr. Nabel's previously approved HIV protocol). Mr. Capron suggested that if there is 
a misunderstanding on the part of the IRB, the RAC should clarify the issue. Dr. 
Parkman agreed that the risk/benefit ratio argues against mandatory AZT treatment for 
patients who do not need the drug. Dr. Poeschla stated that the rabbit pyrogen test 
required by his IRB is neither sensitive nor specific. Although the activated lymphocytes 
may produce cytokines that are pyrogenic, the fever experienced by patients can be 
readily treated with medication. Regarding how the number of patients was selected. Dr. 
Poeschla said that is not critical because this is a Phase I trial to compare survival of 
lymphocytes within the same individual. 
Regarding questions about the Informed Consent document. Dr. Poeschla agreed to the 
changes suggested by Dr. Carmen. As to the directive made by patients to consent for 
autopsy irrespective of a relative's objection. Dr. Poeschla said that this language is 
requested by most of his HIV( + ) patients. In regard to the question of any potential 
benefit to the patients, Dr. Poeschla said that considering the small number of cells to be 
administered to patients, the clinical benefit is very small, and it will be stated clearly in 
the Informed Consent that there will be no clinical benefit. In future trials, the use of 
stem cells may have a greater potential to affect disease progression. 
Dr. Hirano stated that a rehearsal scale-up experiment must be performed to ensure that 
lymphocytes obtained from HIV( + ) patients are transduced with the vector, enriched by 
G418 selection, checked for lack of HIV, and grown up to clinical quantity. 
Dr. Straus suggested that a letter be forwarded from ORDA to the IRB recommending 
that AZT administration and rabbit pyrogen testing should not be mandatory. 
Committee Motion 
A motion was made by Dr. Straus and seconded by Dr. Chase to approve the protocol 
contingent on the following: (1) a letter will be forwarded from ORDA to the IRB 
Recombinant DNA Research, Volume 18 
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