Recombinant DNA Advisory Committee - 03/1-2/93 
received only a single treatment of either 4-HC or 11-2. Dr. Brenner responded that 
although the patients may benefit from a single treatment, it is unknown which is the 
most efficacious method. There is no data demonstrating that either of these treatments 
alone or in combination is effective. Dr. Leventhal said that parallel studies with single 
vectors and purging methods would require a larger number of patients than this 
simultaneous labelling experiment. 
Dr. Leventhal asked how the investigators are interpreting the data which demonstrates 
80% gene marking in patients who are still in remission. Dr. Brenner responded that 
they are transducing a long-lived progenitor cell, if not a pluripotent stem cell. This 
assumption is based on GEMM colonies growing out at 1 year as well as marking of T 
and B cells. Four of these patients have an A21 translocation. Other patients have 
demonstrated CD34 and CD 56 double positive cells. In the neuroblastoma study, 2 
patients have relapsed, 1 of which was marked. Dr. Parkman asked if the neuroblastoma 
relapse was at the original site of disease. Dr. Brenner said that biopsies are currently 
being analyzed; therefore, the only known site of relapse at this time is the marrow. 
Committee Motion 
A motion was made by Dr. Chase and seconded by Dr. Haselkorn to approve the 
protocol. The protocol was approved by a vote of 17 in favor, 0 opposed, and no 
abstentions. 
HI. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: A PHASE I TRIAL OF HUMAN GAMMA 
INTERFERON-TRANSDUCED AUTOLOGOUS TUMOR CELLS INPATIENTS WITH 
DISSEMINATED MALIGNANT MELANOMA /DR. SEIGLER 
Review--Dr. Leventhal 
Dr. Walters called on Dr. Leventhal to present her primary review of the protocol 
submitted by Dr. Hilliard F. Seigler of Duke University Medical Center, Durham, North 
Carolina. 
Dr. Leventhal provided a brief overview of the proposed study. This protocol is a Phase 
I trial of human gamma interferon (Y-IFN)-transduced autologous tumor cells in patients 
with disseminated malignant melanoma. Autologous tumor cells will be grown in short- 
term culture and transduced with the gene encoding for y-IFN. Patients will receive 
subcutaneous injections of 3 x 10 7 transduced irradiated tumor cells every 2 weeks for 3 
months and 1 injection per month for a total of 24 injections. 
Animal data has been submitted demonstrating that transduced cells grow at a slower 
Recombinant DNA Research, Volume 17 
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