Recombinant DNA Advisory Committee - 06/1-2/92 
In conclusion, Dr. Brenner presented data demonstrating the duration of ex vivo lLr2 
expression in neuroblastoma clones derived from several patients. IL-2 production 
following G418 selection is proportional to IL-2 expression in selective media. G418 
selected clones were cultured for three weeks with and without G418. Clones that were 
cultured in non-selective G418 media exhibited only a 25% decrease in IL-2 production. 
Patients will undergo biopsies two weeks following treatment. Dr. Brenner anticipates 
that the tumors will be destroyed at two weeks; therefore, the slight decrease in IL-2 
expression over time is insignificant. 
Committee Motion 
Dr. Leventhal moved to approve the protocol contingent on the following stipulations: 
(1) the informed consent document will include a statement regarding protectidn of the 
patient from publicity, (2) the informed consent document will include a request for 
autopsy in the event of death, and (3) the IL-2 retroviral vector will be assayed in human 
neuroblastoma cell lines to verify that no oncogenic virus is rescued. Mr. Capron 
seconded the motion. 
The motion to approve the protocol passed by a vote of 19 in favor, 0 opposed, and no 
abstentions. 
V. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING 
A HUMAN GENE THERAPY PROTOCOL ENTITLED GENE THERAPY FOR THE 
TREATMENT OF BRAIN TUMORS USING INTRA-TUMORAL TRANSDUCTION 
WITH THE THYMIDINE KINASE GENE AND INTRAVENOUS GANCICLOVIR /DR. 
OLDFIELD: 
Review-Dr. D. Miller 
Dr. Murray called on Dr. D. Miller to present his review. Dr. D. Miller presented an 
overview of the protocol submitted by Drs. Oldfield, Ram, Blaese, and Culver of the 
National Institutes of Health, Bethesda, Maryland. The protocol involves the direct 
injection of a mouse cell line that has been transduced with a retroviral vector containing 
the thymidine kinase (TK) gene into human brain tumors. Dr. D. Miller stated that the 
investigators responded to all of his initial concerns. This protocol is innovative and the 
data is compelling. 
Dr. D. Miller noted that the investigators submitted additional animal data in response 
to comments by the primary and secondary reviewers. These animal experiments 
demonstrate that transduced murine cells persist for an extended period of time in the 
brain and that these cells do not cause overt disease in these animals. 
Recombinant DNA Research, Volume 15 
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