Recombinant DNA Advisory Committee - 12/2-3/93 
passed by a vote of 14 in favor, 0 opposed, and 3 abstentions. 
VIII. CONTINUATION OF DISCUSSION REGARDING A HUMAN GENE TRANSFER 
PROTOCOL ENTITLED: A PHASE I CLINICAL TRIAL TO EVALUATE THE 
SAFETY AND EFFECTS IN HIV- 1 INFECTED HUMANS OF AUTOLOGOUS 
LYMPHOCYTES TRANSDUCED WITH A RIBOZYME THAT CLEAVES HIV-1 
RNA/ DR. WONG-STAAL (SEE PREVIOUS DISCUSSION UNDER CALL TO ORDER) 
Dr. Parkman noted that the approval of Dr. Wong-Staal's human gene transfer protocol 
was contingent on the University of California, San Diego IRB eliminating the 
requirement for mandatory AZT administration. The transcripts of the September 9-10 
meeting were reviewed, and this contingency was verified. ORDA noted that a letter of 
response has not yet been received from Dr. Wong-Staal's IRB. 
IX. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: INJECTION OF COLON CARCINOMA 
PATIENTS WITH AUTOLOGOUS IRRADIATED TUMOR CELLS AND 
FIBROBLASTS GENETICALLY MODIFIED TO SECRETE INTERLEUKIN-2 /DRS. 
SOBOL AND ROYSTON 
Review-Dr. Miller 
Dr. Walters called on Dr. Miller to present his primary review of the protocol submitted 
by Drs. Robert E. Sobol and Ivor Royston of the San Diego Regional Cancer Center, 
San Diego, California. 
Dr. Miller explained that this Phase I study involves the injection of a mixture of 
autologous irradiated tumor cells and autologous irradiated IL-2-producing fibroblasts to 
stimulate antitumor immune responses in colon carcinoma patients. The fibroblasts will 
be engineered to produce IL-2 by using a replication-defective retroviral vector similar to 
other vectors that have been approved previously by the RAC. The proposal is well 
designed and addresses most issues related to the use of recombinant DNA in humans. 
The investigators have submitted preclinical data derived from the CT26 BALB/c 
colorectal carcinoma murine model. 
Dr. Miller stated that the data does not entirely support the protocol, especially 
regarding the generation of systemic antitumor immunity. Although immunity was 
observed at a concentration of 100 units of IL-2/24 hours, antitumor immunity was not 
demonstrated at doses up to 1,700 units of IL-2/24 hours. The animal model is 
irrelevant because the murine studies employed non-irradiated IL-2-secreting fibroblasts. 
The human study involves irradiated IL-2-secreting fibroblasts. Have experiments been 
conducted with animals that have established tumors? Why is there low viability when 
the IL-2 secreting fibroblasts are irradiated at 3,000 rads? He stated that if these 
concerns are adequately addressed by the investigators, the protocol should be approved 
on the basis that generation of antitumor immune responses may hold promise for the 
treatment of human cancers, and the use of irradiated cells presents minimal risk to the 
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