Human Gene Therapy Subcommittee - 7/30/90 
endpoints of in vitro studies will lead them to studies in human 
beings. He said that establishing safe and efficient gene 
transduction protocols in vitro prior to embarking on the patient 
study is critical. 
Dr. Mulligan said the investigators acknowledge that the amount 
of knowledge to be gained from the study will depend on the 
efficiency of transduction and the clonality of relapsing cells. 
He noted that the investigators and their institution possess the 
necessary expertise and facilities to carry out the proposed 
studies, but recommended deferring approval of the protocol until 
such time as the in vitro experiments could be completed and 
presented. 
Mr. Brewer said the local IRBs had given the investigators 
provisional approval "to explore the concept only," and he said 
he did not know what additional information they were seeking. 
Further, he said that much of the detail of the TIL portion of 
the experiment was incorporated only by reference in this 
proposal. He felt it would better serve the review by being 
spelled out, at least in summary form within the protocol. Also 
he noted there was no consent form attached to the protocol. 
Mr. Brewer questioned the additional risk to patients of having 
30% more marrow harvested, plus the increased time required for 
this additional harvest. He said that issues of patient rights 
and patient confidentiality needed to be more clearly spelled 
out, as well as issues of stopping criteria in the case of 
adverse effects of treatment. 
Mr. Brewer completed his comments by noting that since three 
different disease entities were being contemplated for treatment 
with different inclusion/exclusion criteria, separate protocols 
and consent forms would be needed for each entity. Further, if 
the gene marking would have an explicit or even an indirect 
effect on the inclusion/exclusion criteria, this issue should be 
looked at in depth before granting approval. 
Dr. Parkman said he felt the use of 4HC (a derivative of 
cyclophosphamide) to purge cells would eliminate target cells for 
insertion of the vector and therefore would require some in vitro 
evidence that the vector could be inserted in effective amounts. 
Further, he said that he would like to see separate protocols 
developed for each disease and that a protocol be brought back 
that was more focused, with more preclinical data showing the 
investigators ability to insert the retroviral vector into 
neoplastic target cells. 
Recombinant DNA Research, Volume 14 
[97] 
