Recombinant DNA Advisory Committee - 09/9-10/93 
relevant. Dr. Parkman inquired about the number of cells that were used for the 
previous CMV study. Dr. Riddell answered that the highest dose of cells administered 
was 1 x 10 9 cells/m , and this dose was well tolerated. With regard to the future course 
of this study, Dr. Riddell explained that if no toxicity or positive antiviral effects are 
observed, the study will progress to a Phase II efficacy trial that will involve a statistically 
meaningful cohort of patients. 
Mr. Capron suggested the addition of a sentence to the Informed Consent document that 
explains the use of the suicide gene more clearly. The investigators appreciated Mr. 
Capron's comments and agreed to incorporate the suggested change. 
Committee Motion 
A motion was made by Dr. Straus and seconded by Mr. Capron to approve this major 
amendment. The motion passed by a vote of 16 in favor, 0 opposed and 2 abstentions 
(Drs. Miller and Motulsky abstained from voting because they are employed by the 
University of Washington). 
VII-A. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: GENE THERAPY FOR RECURRENT 
PEDIATRIC BRAIN TUMORS /DRS. KUN, SANFORD, BRENNER, HEIDEMAN AND 
OLDFIELD 
Review-Dr. Geiduschek 
Dr. Walters called on Dr. Geiduschek to present his primary review of the protocol 
submitted by Drs. Larry E. Kun, R. A Sanford, Malcolm Brenner, and Richard L. 
Heideman of St. Jude Children's Research Hospital, Memphis, Tennessee, and Dr. 
Edward H. Oldfield of the NIH, Bethesda, Maryland. This gene therapy protocol 
involves HSV-tk gene transduction of brain tumor cells followed by administration of the 
antiviral drug ganciclovir. This Phase I trial will involve 6 children > 3 years of age with 
progressive or recurrent malignant supratentorial brain tumors that are resistant to 
standard therapy. Patients will receive multiple intratumoral injections of between 10 8 
and 10 9 murine cells (PA317) in a volume of 1 to 20 milliliters. Patients will be injected 
with the PA317 vector producing cells (VPC) containing the GITKSvNa retrovirus 
vector. Seven days post injection, patients will receive ganciclovir administration for the 
ablation of transduced tumor cells. Anti-tumor responses will be monitored for more 
than one year by magnetic resonance imaging (MRI). This Phase I toxicity study is 
similar to other protocols that have previously been approved by the RAC except for a 
variation in the surgical procedures that are proposed to deliver the VPC. Dr. 
Geiduschek noted his concern about the repetitiveness of such studies. Is the public and 
the progress of gene therapy at this stage best served when a substantial fraction of the 
still small group of investigators focus quasi-repetitively on a single idea? 
Review-Dr. DeLeon 
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Recombinant DNA Research, Volume 18 
