Recombinant DNA Advisory Committee - 06/7-8/93 
performing quantitative PCR analysis and stated that adequate control experiments have 
not been included. Dr. Post said that this proposal has many shortcomings. 
Committee Motion 
A motion was made by Dr. Dronamraju and seconded by Dr. Parkman to defer approval 
of the protocol based on the following concerns: (1) data demonstrating efficient 
transduction of TIL, (2) insufficient information regarding demonstration of selectivity, 
i.e., specific trafficking of TIL to tumor, (3) incomplete statistical analysis, (4) the 
Informed Consent document must be revised in simplified language, and (5) concerns 
about patient responsibility for research-related costs must be addressed. The motion to 
defer approval of the protocol passed by a vote of 18 in favor, 0 opposed, and no 
abstentions. 
XXI. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: IMMUNIZATION OF MALIGNANT 
MELANOMA PATIENTS WITH INTERLEUKIN-2-SECRETING MELANOMA CELLS 
EXPRESSING DEFINED ALLOGENEIC HISTOCOMPATIBILITY ANTIGENS /DRS. 
DAS GUPTA, COHEN AND RICHARDS 
Review-Dr. Smith 
Dr. Walters called on Dr. Smith to present his primary review of the protocol submitted 
by Drs. Tapas K. Das Gupta and Edward P. Cohen of the University of Illinois College 
of Medicine, Chicago, Illinois, and Dr. Jon M. Richards of the University of Chicago, 
Chicago, Illinois. Dr. Smith stated that this protocol is a Phase I study of 12 patients 
with advanced stage melanoma. Patients will be injected with a melanoma cell line 
(Mel-4) that has been transduced with a gene encoding IL-2. These transduced cells will 
act as an immunogenic vaccine. The hypothesis is that IL-2 secreting allogeneic 
melanoma cells will induce B and T cell anti-tumor responses. The endpoint for this 
study is toxicity; however, minor endpoints will include measurements of the induction of 
antibodies against HLA and melanoma associated antigen, and where possible, induction 
of CTL-mediated responses and other parameters. The transduced Mel-4 cells will be 
irradiated with 10,000 rads. He stated his concern that the murine data was generated 
using viable melanoma cell immunization; however, the human study proposes using 
irradiated cells that could impair IL-2 secretion. Is IL-2 production in Mel-4 cells stable 
following irradiation? What are the levels of IL-2 production in human cell lines? Dr. 
Smith stated that he was originally concerned that the eligibility criteria in this protocol 
were too stringent, but the PI has relaxed the criteria. The Informed Consent document 
implies that the purpose of this trial is therapeutic, yet requires patients to pay for part 
of the research associated costs. This issue must be addressed by the Pis. In summary, 
additional information regarding the background data, particularly the transduced cell 
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Recombinant DNA Research, Volume 17 
