Human Gene Therapy Subcommittee - 11/21-22/91 
Greenberg stated that the effects would be indistinguishable. By providing informed 
consent, the patient assumes responsibility for the cost of clinical care resulting from 
illness. Dr. Walters asked if an attempt would be made to bill the third party carrier 
first. Dr. Greenberg agreed that insurance companies will be billed first; however, the 
patient is ultimately responsible. 
Dr. Miller inquired as to whether the patient's participation in this protocol affects their 
ability to obtain insurance for the remainder of the treatment. Dr. Greenberg stated 
that he could not answer the question definitively; however, historically at the Fred 
Hutchinson Cancer Center, third party carriers agree to coverage following participation 
in more than one experimental protocol. 
Dr. Miller requested that the investigators provide a list of assays that will be performed. 
Dr. Overell presented a summary slide of the validation testing including sterility, 
mycoplasma, transmissional electronmicroscopy with and without iodo-deoxyuridine 
treatment, karyology, soft agarose tumorigenicity, MAP testing, and screening for bovine 
and porcine viruses. Southern blot analysis is performed to verify the integrity of the 
viral structure and viral titer is always determined. Amplifications are performed for the 
detection of replication-competent helper virus. 
PROPOSED AMENDMENT TO APPENDIX D OF THE NIH GUIDELINES 
REGARDING A HUMAN GENE THERAPY PROTOCOL ENTITLED 
LYMPHOKINE GENE THERAPY OF CANCER: PHASE I STUDY OF 
TUMOR IMMUNOTHERAPY WITH AUTOLOGOUS FIBROBLASTS 
GENETICALLY MODIFIED TO SECRETE INTERLEUKIN-2 /Hr. Sobol: 
Review-Dr. Parkman 
Dr. Walters called on Dr. Parkman to present his primary review of the protocol 
submitted by Dr. Robert Sobol of the San Diego Regional Cancer Center, University of 
California, San Diego, California. Dr. Parkman explained that the protocol is derived 
from basic research demonstrating that the insertion of the gene coding for IL-2 
expression into mice results in a more effective immune response. The data that provide 
the basis for this protocol are the same data used by Dr. Steven Rosenberg of the 
National Cancer Institute, NIH, to support his gene therapy protocol. The HGTS and 
the RAC have previously reviewed and approved Dr. Rosenberg's protocols. Dr. 
Rosenberg proposed to insert the IL-2 gene and the TNF gene into human cells. The 
only difference between Dr. Sobol's protocol and Dr. Rosenberg's protocol is that Dr. 
Sobol is proposing to obtain a skin biopsy from the patient, grow the fibroblasts in vitro , 
mix the fibroblasts with irradiated tumor cells, and inject the mixture subcutaneously. 
Dr. Rosenberg proposed transducing tumor cells with genes coding for either IL-2 or 
TNF and injecting these viable tumor cells into patients. The question is whether the 
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