Recombinant DNA Advisory Committee - 03/1-2/93 
A motion was made by Dr. Parkman and seconded by Ms. Grossman to defer approval 
of the protocol. There was a brief discussion between RAC members in which they 
agreed that Dr. Bank had not demonstrated transduction in the reconstituting cell 
population that would ultimately be administered to the patient. Although transduction 
data was submitted using the murine stem cells, the same transduction protocol was not 
used. Dr. Bank noted that he has successfully transduced CFU-GEMM cells. Dr. 
Leventhal said that the CFU-GEMM data was not submitted to the RAC. Dr. Parkman 
stated that additional data should have been submitted demonstrating the effect of the 
proposed dose of Taxol following ABM transplantation. Safety must be demonstrated 
with the proposed vector. Dr. Leventhal stated that data should be obtained 
demonstrating transduction of CD34( + ) cells in a "macro" system. 
Dr. Michael Gottesman, a co-investigator, commented that there is an implicit 
assumption that the MDR gene has to be inserted into stem cells in order to provide 
protection. Short-term protection by active cells might be equally as effective in 
providing protection against the chemotherapeutic agents as stem cells; particularly since 
stem cells already exhibit a slight degree of MDR protection. One of the goals of this 
protocol is to determine whether the MDR gene will be inserted into stem cells. 
Therefore, failure to demonstrate transduction of stem cells is not a valid reason for 
disapproval of this protocol. Dr. Parkman stated that the objectives of the protocol had 
not been presented in this manner. If the protocol was designed as a trafficking study to 
determine which cell populations are transduced by this procedure, the RAC may have 
approved the study as a legitimate protocol. The protocol has not been written with this 
intent. Dr. Leventhal agreed with Dr. Parkman and noted that endpoints are the real 
issue. If stem cell transduction is demonstrated, the patients could probably receive 
several courses of Taxol. If committed progenitor cells are transduced, patients may 
require ABM transplantation after each course of Taxol. 
Approval of the protocol is deferred until the investigators provide the following 
additional information for full RAC review: (1) safety data, e.g., S + L' assays 
demonstrating the absence of RCR using the proposed vector, PHaMDRl/A and the 
amphotropic retrovirus packaging line, GP+envAM-12: (2) toxicity data demonstrating 
the effect of Taxol, at doses comparable to those proposed in the protocol, in patients 
undergoing ABM transplantation; and (3) transduction of CD34( + ) bone marrow cells in 
a large animal model or long-term bone marrow culture. 
The motion to defer approval of the protocol was approved by a vote of 20 in favor, 0 
opposed, and no abstentions. 
V. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: ADMINISTRATION OF NEOMYCIN 
RESISTANCE GENE MARKED EBV SPECIFIC CYTOTOXIC T LYMPHOCYTES TO 
Recombinant DNA Research, Volume 17 
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