Recombinant DNA Advisory Committee - 06/7-8/93 
should demonstrate whether IU2 is produced at 24, 48, or 72 hours following irradiation 
with 10,000 rads. Dr. Miller suggested that data be submitted demonstrating that 5,000 
rads inactivates the growth of human cells and that these cells continue to secrete IL-2. 
Dr. Post recommended that RCR co-cultivation assays should be submitted using 
irradiated human cells. Dr. Miller added that a positive control experiment 
demonstrating RCR in human melanoma cells will aid in the interpretation of RCR 
assays on these cells. Dr. Miller said that he had screened the vector sequence through 
GenBank, and that no harmful sequences or open reading frames were identified. 
Committee Motion 
A motion was made by Dr. Smith and seconded by Ms. Grossman to defer approval of 
the protocol until the investigators return to the RAC with the following: (1) data 
demonstrating the efficiency of transduction in Mel-4 cells; (2) data demonstrating 
viability, IL-2 production, and in vivo murine effect of irradiated transduced cells (either 
5,000 or 10,000 rads); (3) rationale for ethnic eligibility criteria; (4) complete responses 
to the Points to Consider; and (5) RCR testing data demonstrating safety of the vector 
preparation. The motion to defer approval of the protocol passed by a vote of 19 in 
favor, 0 opposed, and 1 abstention. 
XXII ADDITION OF APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: HUMAN MDR GENE TRANSFER IN 
PATIENTS WITH ADVANCED CANCER/ DRS. HESDORFFER AND ANTMAN 
Review-Dr. Parkman 
Dr. Walters called on Dr. Parkman to present his primary review of the protocol 
submitted by Drs. Charles Hesdorffer and Karen Antman of Columbia University 
College of Physicians and Surgeons, New York, New York. Dr. Parkman stated that this 
protocol is a resubmission of a proposal previously submitted by Dr. Arthur Bank at the 
March 1993 RAC meeting. The objective of this protocol is to evaluate expression of 
MDR-1 in the progeny of CD34( + ) bone marrow stem cells in recipients of autologous 
bone marrow (ABM) transplants for the treatment of advanced cancer. Patients will be 
followed after ABM transplantation to evaluate MDR-1 expression. At the time the 
original protocol was submitted, the RAC was concerned about clinical aspects of the 
protocol. The original protocol was approved for the non-invasive treatment of 
melanoma. Ovarian, brain, and breast cancer are the proposed targets of this study. 
The Pis have submitted additional data demonstrating the lack of RCR using co- 
cultivation with Mus dunni. The Pis have removed all aspects concerning the post- 
transplant administration of Taxol from the protocol. The revised protocol focuses on 
the transduction of CD34( + ) cells rather than "human hematopoietic stem cells." The 
Informed Consent document has been revised. Since Taxol administration is no longer 
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Recombinant DNA Research, Volume 17 
