Recombinant DNA Advisory Committee - 03/1-2/93 
CD34( + ) cells will be grown in Dexter culture. Transduced MDR sequences can be 
distinguished from PCR endogenous sequences by this method. MDR-resistant cells will 
be enriched following each consecutive cycle of Taxol. A correlation will be made 
between the number of MDR transduced cells and the level of chemotherapy-induced 
neutropenia. Patients will be monitored following each dose of Taxol. 
Dr. Deisseroth presented in vivo murine data. Data demonstrated that transduced bone 
marrow cells conferred a protective effect against Taxol. Dr. Miller noted that the 
vector used in the animal model is different from the vector proposed for the human 
study. Dr. Deisseroth acknowledged that the 2 vectors are different. Another objection 
made by Dr. Miller is that 5FU, which was used to enrich stem cells in the animal study, 
will not be used for human studies, a significant difference. Dr. Deisseroth presented 
preliminary data showing a protective effect of the vector that will be used in the human 
trial in the murine model. Drs. Miller, Leventhal, and Parkman all commented that this 
data should have been submitted with the protocol. 
Dr. Post commented that there was no quality control data on the packaging cell line. 
Dr. Parkman expressed his concern that the potential risk to patients has not been 
adequately stated in the informed consent document, i.e., the risks associated with Taxol 
administration alone and in combination with transduced and untransduced ABM cells. 
If patients suffer from neutropenia, they may require transplantation of the 
cryopreserved marrow and a long costly hospital stay. Dr. Deisseroth conceded that the 
protocol may have to be revised incorporating a lower dose of Taxol in order to reduce 
the risk to patients. 
Committee Motion 
A motion was made by Dr. Leventhal and seconded by Dr. Parkman to defer approval of 
the protocol. Approval is deferred until the investigators return to the RAC with the 
following: (1) additional preclinical data on the infusion of CD34( + ) ABM cells, (2) 
data demonstrating safety of the starting dose of Taxol, (3) a clear description of the 
proposed vector, (4) a revised informed consent document using simplified language and 
including a statement about the potential risks associated with Taxol administration 
following ABM transplantation (5) a revised title reflecting the fact that early progenitor 
cells will be used rather than stem cells, and (6) provide long-term cell culture data. The 
motion to defer approval of the protocol passed by a vote of 16 in favor, 0 opposed and 
no abstentions. 
VI. ADDITION TO THE POINTS TO CONSIDER OF THE NIH GUIDELINES 
REGARDING PROCEDURES FOR EXPEDITED REVIEW OF HUMAN GENE 
TRANSFER PROTOCOLS (CONTINUED) 
Recombinant DNA Research, Volume 17 
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