Recombinant DNA Advisory Committee - 2/10-11/92 
cells that can progress from a very undifferentiated stage to totally differentiated T 
lymphocytes or granulocytes; it is entirely possible that some of these stem cells were 
transduced with the ADA gene in the original protocol although there is no direct 
evidence. Currently, the patients are demonstrating a positive clinical response. This 
response could be due in part to the transduction of stem cells. However, the fact remains 
that the tests for immune function are not entirely normal. Thus, the current proposal is 
designed to enhance the likelihood that the more undifferentiated cells can be transduced 
and that such cells will have a positive growth advantage. By using the G1SAX vector, it 
will be possible to determine later on whether or not the patients' T lymphocytes contain 
one or both vectors, and that would indicate the stage of differentiation and growth. 
Dr. Leventhal asked if the CD34(+) cells could be reconstituted. Then the question was 
raised whether it would be more advantageous to continue using T lymphocytes. She 
stated that the RAC was disappointed that the first two patients who participated in the 
original study were being proposed to receive treatment in the amended protocol. Dr. 
Anderson clarified that the protocol would also be applied to other patients. Currently, a 
third patient is being recruited, and others will be recruited as they become available. 
Dr. Krogstad asked the FDA to comment on whether or not all of the safety criteria had 
been satisfied with regard to the new vector. Dr. H. Miller responded that he did not 
know whether the protocol review, including the vector, had been completed by the Center 
for Biologies; therefore, he could not comment at this time. Dr. McGarrity stated that the 
GIN system had been approved by RAC reviewers and the FDA, and this system has been 
used in neuroblastoma patients at St. Jude's Hospital. 
Mr. Barton pointed out that he would be more comfortable if a Points to Consider 
response had been completed which would clarify what tests had not been performed, what 
the subjects would be like, who they would be, and how the patients would be chosen. 
This information should be made available at the next meeting, and the RAC could 
possibly approve the protocol at that time. Dr. Anderson responded that the covering 
memo addressed those issues in the Points to Consider that were different, and that 
everything else was identical. He acknowledged that the information should have been 
placed in a Points to Consider format. 
Dr. Carmen asked if there was any increased risk to the patients resulting from the new 
undifferentiated target cells being transduced. Dr. Anderson stated that the risk to the 
patient would be increased by a factor of two because there were now two populations of 
cells being administered. The risk from the T lymphocytes was determined to be about 
10' 14 , so the additional risk of adding the CD34 selected transduced cells would be about 
2x1 0‘ 14 . 
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Recombinant DNA Research, Volume 15 
