July 30, 1990, Human Gene Therapy Subconmi ttee 
investigators are interested in obtaining both infection of cells required for successful 
engraftment to keep the patient alive and malignant cells potentially to be found in the 
bone marrow inoculum. He said that transduction protocols must be considered within 
the framework of the ABMT therapy and that transduction should neither interfere with 
the ability of the bone marrow cells to reconstitute, nor increase the frequency and/or 
growth potential of any tumor cells in the marrow sample. 
Dr. Mulligan said that feasibility studies needed to be elaborated in more detail, 
particularly with respect to assays to be employed in assessing effects of specific culture 
conditions on progenitor and tumor cell growth. Further, he said the investigators need 
to clarify in more detail what successful 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 
[204] 
Recombinant DNA Research, Volume 14 
