Recombinant DNA Advisory Committee - 2/10-11/92 
VI. 
vaccines. The public would receive conflicting messages if the RAC and the FDA vote 
differently. Dr. Geiduschek stated that the RAC's task is to review clinical gene therapy 
protocols for: (1) adherence to the NIH Guidelines', (2) principles of informed consent; (3) 
degree of preparation; (4) coherence quality; and (5) likelihood of scientific contribution to 
the field of human gene therapy. Dr. Geiduschek said that these protocols undergo a 
more rigorous review process by the RAC than by the FDA. At the FDA, protocols are 
judged in coherence with other clinical protocols. The RAC judges these clinical trials 
individually on their own merits. 
Dr. Mclvor moved that the motion to approve this protocol be amended to reflect the 
RAC's concerns about safety. Transduced, irradiated cells must be assayed for the 
production of replication-competent helper viruses and the generation of rescued TK virus. 
Dr. Mclvor's amendment was seconded by Dr. Gellert. The motion to approve the 
amendment passed by a vote of 14 in favor, 0 opposed, and no abstentions. The motion to 
approve the protocol was passed by a vote of 10 in favor, 4 opposed, and no abstentions. 
PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING 
HUMAN GENE THERAPY PROTOCOL ENTITLED: IMMUNOTHERAPY OF 
MALIGNANCY BY IN VIVO GENE TRANSFER INTO TUMORS 
Review-Dr. Haselkorn 
Dr. Haselkorn reviewed the protocol submitted by Dr. Nabel stating that DNA has been 
successfully injected directly into animal tissues. Dr. Nabel proposes to use techniques to 
insert DNA into human melanoma cells, a procedure that has not been reviewed 
previously by the RAC. Dr. Nabel requests permission to inject liposome-encapsulated 
DNA molecules directly into the tumor. The expectation is that the conversion of a small 
percentage of melanoma cells to express the HLA-B7 antigen will stimulate an immune 
response, thus destroying the tumor. 
Dr. Haselkorn said that he had several technical questions: (1) Will circular or linearized 
DNA be used; if it is linearized, how will it be stored? (2) How will the optimal 
composition of the DNA/liposome complex be determined? (3) How will the effects on 
metastases be evaluated? (4) What are the immunological consequences of the mouse 
experiments with Class I MHC surface protein and the transport of DNA in the nervous 
system? (5) Will patients be immunized with HLA-B7 before the DNA transfer? and (6) 
How will a destructive immunological response be mounted if only 1% of the cells in the 
tumor express the HLA-B7 surface antigen? 
Review-Dr. Murray 
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