Recombinant DNA Advisory Committee - 06/7-8/93 
necessity for fresh cord blood is the basis for this minor modification. 
Committee Motion 
A motion was made by Dr. Post and seconded by Dr. Motulsky to approve the minor 
modification allowing for the treatment of ADA-deficient newborns with autologous 
CD34( + ) cells obtained from the cord blood and placenta. Also, this modification will 
allow the Pis to: (1) withdraw PEG-ADA at their discretion, and (2) perform bone 
marrow aspirations, as necessary, to monitor for gene transduction. The motion passed 
by a vote of 18 in favor, 0 opposed, and 3 abstentions. 
VIII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: IMMUNOTHERAPY FOR CANCER BY 
DIRECT GENE TRANSFER INTO TUMORS /DR, NABEL 
Review-Dr. Doi 
Dr. Walters called on Dr. Doi to present his primary review of the protocol submitted by 
Dr. Gary J. Nabel of the University of Michigan Medical Center, Ann Arbor, Michigan. 
This protocol is an extension of the study approved by the RAC at its February 1992 
meeting. The goal of this protocol is to improve the efficacy of tumor immunotherapy 
by the introduction of a gene encoding a foreign Class I MHC protein. The investigators 
propose that enhanced production of this protein will augment a CTL response against 
unmodified tumor cells. This protocol incorporates modifications that were not part of 
the original protocol approved by the RAC. These changes include: (1) the use of 
more efficacious cationic liposomes in which l,2-dimyristyloxypropyl-3-dimethyl- 
hydroxyethylammoniumbromide (DMRIE) is utilized with dioleoyl- 
phosphatidylethanolamine (DOPE) for more efficient delivery of the gene; (2) the use of 
an improved vector, which includes the (12 microglobulin gene that forms a complete 
complex with Class I MHC gene product; (3) the inclusion of a catheter-based gene 
delivery system for direct gene transfer into the tumor microcirculation; and (4) 
application of the system to different tumor types. Preliminary murine data indicate that 
the new DMRIE/DOPE liposome preparation: (1) improves transfection efficiency, (2) 
demonstrates minimal toxicity, and (3) enhances the anti-tumor effect against the foreign 
MHC gene. Dr. Doi posed the following questions: (1) Has liposome transfection 
proved to be safe and efficacious in the previous RAC-approved protocol? (2) Have 
anti-tumor effects been observed? (3) Have all of the previous safety and toxicity 
concerns been satisfactorily resolved? (4) Will the increased transduction efficiency in 
vitro with DMRIE/DOPE be reproducible in vz'vo? (5) Are there any possible adverse 
effects on the immune response to DMRIE/DOPE? (6) How precise is the catheter 
delivery? (7) Will normal cells be transduced? and (8) What is the discomfort level in 
patients undergoing catheter administration? If the investigators can satisfactorily 
[558] 
Recombinant DNA Research, Volume 17 
