Recombinant DNA Advisory Committee- 9/12-13/94 
Robert Sobol and Ivor Royston in 1993. Mr. Capron expressed his support of the concept 
of consolidated review. 
Responding to a question by Ms. Meyers about public access to the information, Ms. 
Wilson (ORDA) explained that for those IND applications submitted to FDA but not 
reviewed by the RAC, the public portions of the INDs including Points to Consider and 
Informed Consent document will be kept at the ORDA and will be made publicly 
accessible. The protocols will be tracked by using the FDA’s IND numbers. Dr. Noguchi 
said this public accessibility is the aspect that FDA by law cannot do by itself. He 
proposed an FDA/ORDA/RAC working group to address problems of long-term 
consolidation. 
Dr. Walters said that the discussion on the proposal for NIH/FDA consolidated review 
will resume tomorrow morning, and the RAC should achieve cloture for a final vote. 
XI. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: A PILOT STUDY OF AUTOLOGOUS 
HUMAN INTERLEUKIN-2 GENE MODIFIED TUMOR CELLS INPATIENTS WITH 
REFRACTORY OR RECURRENT METASTATIC BREAST CANCER /DR. LYERLY 
Review-Dr. Smith 
Dr. Walters called on Dr. Smith to present his primary review of the protocol submitted 
by Dr. H. Kim Lyerly of Duke University Medical Center, Durham, North Carolina. Dr. 
Walters remarked that the discussion will be divided in two parts: an open session and a 
closed session to discuss the proprietary information regarding the construction of the 
vector and its sequence. This is the second time in the review of gene therapy that the 
RAC has to hold an executive session. The other occasion was when confidential patient 
information was discussed during a single patient expedited review. 
Dr. Smith said that this protocol is another cancer vaccination. This protocol proposes to 
utilize an AAV provirus based plasmid DNA complexed with a cationic liposomal vehicle 
to transduce autologous breast cancer cells with the gene for human EU2. The transduced 
cells will be administered subcutaneously to patients in an accelerating dose schedule for 4 
doses (0.1, 0.5, 1.0, 5.0 x 10 8 cell every 4 weeks for 4 months). The endpoints to be 
assessed include: (1) toxicity, (2) in vitro immunological reactivity to the breast cancer 
cells, (3) duration of clinical response, and (4) patient survival. Patient selection will 
include those with metastatic disease who have failed all conventional therapy. The plan 
would require 20 patients. 
There are two major differences from previously approved protocols: (1) it involves 
breast cancer; and (2) it uses a plasmid DNA derived from the AAV to deliver the IL-2 
gene in a liposome complex. In terms of the disease, it has long been held that breast 
cancer, unlike melanoma and renal cell carcinoma, is not particularly immunologically 
responsive to vaccination therapy. The investigator has provided encouraging preclinical 
data in the mouse model to demonstrate that this approach might be useful in preventing 
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