Recombinant DNA Advisoiy Committee - 2/10-11/92 
back to you end up in your body, but this may be of no direct benefit to you. It may 
help in understanding how to improve the outcome for BMT patients in general, 
particularly those with immunodeficiency disorders." 
Dr. Mclvor accepted the proposed changes of Drs. Carmen and Leventhal as amendments 
to his original motion. Further discussion ensued regarding the issue of separating the 
consent form into two separate forms: one for BMT and one for adoptive immunotherapy. 
After considerable debate, it was agreed by the RAC and Dr. Greenberg that a single 
form would be acceptable with the proviso that there be a clearly defined separate section 
for adoptive immunotherapy. There being no other outstanding issues, the motion to 
approve the protocol was passed by a vote of 16 in favor, 0 opposed, and no abstentions. 
XI. AMENDMENT TO THE ADA PROTOCOL (CONTINUED) 
The RAC returned to the discussion of the proposed amendment to the ADA protocol 
presented the previous day by Dr. Blaese and tabled by the RAC. Dr. Murray reminded 
the RAC that the discussion focused on the issue of whether the protocol should have 
been an entirely new protocol or approved as an amendment to a previously approved 
protocol. Dr. Leventhal was asked to reiterate her previous remarks concerning additional 
information presented. 
Dr. Leventhal stated that the new information confused the goals of the study. The aim of 
the study is to attempt to produce a long-term cell line that will make ADA. As the 
protocol is written, there is no ability to assess the effect of CD34( + ) cells on the immune 
system of the patient because the investigators are already supplying ADA to the patient 
via T-cells. The real goal is to determine whether cells from the CD34 lineage can be 
identified in the peripheral blood, which is not an unreasonable goal. Restoring the 
non-lymphoid hematopoietic cells' ability to produce ADA might improve the immune 
system. The protocol has a reasonable goal which is to select CD34( + ) cells, transduce 
them with the ADA gene, and then scan for progeny in the blood circulation. The 
protocol design seemed satisfactory pending FDA approval of the new vector. 
Dr. Mclvor reiterated that expression in the myeloid and erythroid lineages would only be 
as beneficial as the PEG/ AD A treatment. It would be an extracellular source of enzyme 
for lymphocytes. The investigators still have not shown that they can accomplish 
transduction of cells that are capable of generating lymphocytic lineages and that the 
proposed vector is capable of providing ADA expression after cell differentiation. There 
are no preclinical data demonstrating that the vector could convey ADA expression to 
differentiated cells. Therefore, he could not vote for approval of this amended protocol. 
Ms. Buc asked whether the purpose of the protocol was to track the cells or for 
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