Recombinant DNA Advisory Committee - 2/10-11/92 
therapeutic effect. Dr. Anderson said that the primary purpose of this protocol is therapy. 
Ms. Buc asked what would be the measures of efficacy. Dr. Anderson responded that the 
measures of efficacy would be the same as in the original protocol-immune function 
studies and the clinical studies of the patient. In the amended protocol, the investigators 
will be tracking all the hematopoietic cells, not just the T lymphocytes. Dr. Anderson 
concluded that the only definitive evidence concerning the ability to track the cells will 
come from the patients. 
Dr. Gellert stated that the protocol is searching for positive results in a narrower window. 
Since the current patients are largely reconstituted immunologically, it is unclear how the 
protocol would determine the holes in the immune repertoire. Dr. Anderson responded 
that the investigators have conducted many immune function studies, and most results are 
not within the normal range. These data indicate that there are holes in the immune 
system. The known holes are not dangerous; however, the danger is when the holes 
cannot be found. 
Dr. Dunbar added that there is an indirect method for determining the function of the 
transduced T lymphocytes from the CD34( + ) cells. If the production of T lymphocytes 
marked with the second vector increases over time, there is possibly a selective advantage 
in vivo. This determination shows indirectly an advantage to T lymphocytes that originated 
from transduced CD34( + ) cells. 
Dr. Mclvor disagreed with the motion that the preclinical assessment for transducing 
CD34( + ) cells is at the same stage as the T lymphocyte transduction. T lymphocyte 
transduction was supported by experimental evidence in SCID mice that the ADA 
expression vector provided lymphoid function. There is no comparable evidence for this 
protocol. He asked how the distinction would be made between transduced lymphocytes 
and lymphocytes generated from transduced stem cells. Dr. Anderson stated that detection 
of ADA-B with the G1SAX vector in the granulocyte fraction would give the answer. 
Obviously, the peripheral blood mononuclear cells would have to be fractionated. Dr. 
Dunbar added that cells could be inserted into SCID mice in order to determine if marked 
cells were expressing ADA. This experiment would require collaboration with other 
laboratories. 
Dr. Krogstad said that it is very difficult to judge this protocol as a treatment, although it 
could be valuable as an experiment. After the experiment is conducted, it will be difficult 
to determine whether the treatment has had a therapeutic outcome. Dr. Anderson agreed 
that this procedure may not be therapeutic in the original two patients. In the absence of 
a dramatic improvement, it would be difficult to find therapeutic effect. 
Dr. Culver concurred that the beginning of the protocol is non-therapeutic and only 
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