Recombinant DNA Advisory Committee - 03/1-2/93 
approval. 
Further questions were raised about in vitro studies that were performed for other 
purposes, with 4 tumor cell lines previously established by Dr. Niramol Savaraj, a co- 
investigator. Data on ID-2 production are not complete due to limited life span of these 
cells which already have been in tissue culture for several months. In the future, Dr. 
Savaraj will be responsible for establishing tumor cell lines from biopsies for the gene 
therapy protocol. 
Dr. Dronamraju asked about Dr. Podack's contribution to a paper submitted with this 
protocol regarding combination effect of vaccination with IL-2 and IL-4 complementary 
DNA transfected cells and the induction of a therapeutic immune response against Lewis 
lung carcinoma cells. Dr. Podack stated that this animal model work was initiated while 
he visited the Japanese laboratory at the National Cancer Institute in Japan and was 
performed largely by scientists in that laboratory. In response to Dr. Dronamraju's 
question about IL-2 and IL-4, Dr. Podack stated that if IL-2 experiment is successful, 
then the combination of IL-2 and IL-4 will be used. 
Dr. Parkman summarized the discussion noting that interesting pre-clinical data have 
been provided, but the protocol does not have all the elements to justify approval. Dr. 
Leventhal criticized the protocol for lack of any in vitro human data showing that 
transduced peripheral blood cells from tumor bearing patients demonstrate an enhanced 
anti-tumor response to autologous tumor cells from those patients. Dr. Parkman 
concurred that additional data should be provided using freshly established cell lines 
from tumor biopsies. Drs. Leventhal and Miller requested that an endpoint should be 
included, i.e., CTL assays. Dr. Podack said these studies will be performed in the future. 
Committee Motion 
A motion was made by Dr. Miller 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) a definition of the clinical endpoints, (2) clonogenic assays using irradiated 
tumor cells, and (3) a revised informed consent document, including a statement that 
some patients selected for gene therapy will require a second surgical procedure to 
obtain material for the study. The motion to defer approval of the protocol passed by a 
vote of 18 in favor, 0 opposed, and no abstentions. 
XV. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING 
A HUMAN GENE THERAPY PROTOCOL ENTITLED: USE OF SAFETY-MODIFIED 
RETROVIRUSES TO INTRODUCE CHEMOTHERAPY RESISTANCE SEQUENCES 
INTO NORMAL HEMATOPOIETIC STEM CELLS FOR CHEMOPROTECTION 
DURING THE THERAPY OF OVARIAN CANCER/DR. DEISSEROTH 
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Recombinant DNA Research, Volume 17 
