Human Gene Therapy Subcommittee - 11/21-22/91 
Dr. Mclvor said that it is not necessary to review the entire FDA file. However, the 
HGTS should clarify exactly what test results it expected to see from the investigators 
with regard to new retroviral vectors. The investigators need to present data along with 
the positive controls. Dr. Leventhal noted the mention of "slight changes attributable to 
a higher titer as seen with GINa." These changes need to be specified. 
Dr. Erickson requested additional data on PCR quantitation. Dr. Miller suggested that 
vector sequence data should be provided for comparison to known oncogenes in 
GenBank as well as screening for open reading frames that could potentially encode for 
new proteins. Dr. Miller asked for evidence of the quality of testing that will be 
performed. Dr. McGarrity replied that GTI would provide specific results. 
Dr. Anderson cautioned the HGTS against wanting to examine all of the data that are 
submitted to the FDA; some investigators may not have that option due to concerns 
about confidentiality. Dr. Walters suggested that this information should be made 
available only to the primary reviewers. Dr. Anderson agreed. 
Dr. Parkman said that there was no problem with modifying a basic vector, but that a 
new vector should be presented with all its accompanying data. Dr. Anderson stated that 
GINa was only a minor modification of the LNL6 vector that had previously been 
approved by the HGTS and the RAC. Dr. Mclvor disagreed with Dr. Anderson stating 
that in the development of the GINa vector, a new cell line had been established. 
Safety testing should proceed as with the original vector. 
Dr. Leventhal stated that the issue of confidentiality will be discussed in more detail as 
part of her Working Group on Data Management report. 
Mr. Capron suggested that a vote for approval of this protocol should be conditional 
upon review of the vector safety data. Mr. Capron suggested that the HGTS should 
arrive at a consensus as to additional data that are required and that the Points to 
Consider document should be amended to address specific data requirements for the 
review of new vectors. 
Dr. Epstein commended the investigators on the design of the protocol, noting the 
internally controlled homing experiment. However, additional data should be provided 
concerning the ability to determine the cell ratios using PCR. Reconstruction 
experiments should be performed using known inputs of cell types and markers. The 
data provided demonstrate that no CD4( + ) cells were detectable. Therefore, how will 
the investigators expand and obtain a pure population of CD4( + ) cells? 
Dr. Parkman asked if PBL expanded in IL-2 are similar to lymphokine activated killer 
(LAK) cells. Dr. Economou replied that LAK cells are generated over a shorter time 
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