Human Gene Therapy Subcommittee - July 29-30, 1991 
Dr. Parkman said treatment should be restricted to melanoma, renal cell carcinoma, 
and colon carcinoma patients. 
Dr. Rosenberg asked that treatment not be restricted to tumor types. Dr. Parkman 
replied that the approval of other protocols has required a demonstration of 
transduction and expression for the particular tumor type. If these data on other tumor 
types become available, they can be offered as a minor modification of these protocols 
and reviewed at that time. Dr. D. Miller accepted this friendly amendment. 
Dr. Neiman said that ordinarily a pilot study would be performed to establish basic 
safety parameters before obtaining authorization to treat hundreds of patients. One of 
the safety issues is that the secretion of a cytokine from a particular tumor cell could 
conceivably change the phenotype of that cell in an unpredictable and unsafe manner. 
Biologically, tumor cells vary in terms of their behavior. He proposed an amendment 
to Dr. D. Miller's motion which would limit the number of patients initially treated and 
require a safety report for each tumor cell type before full authorization for a 
therapeutic trial with 14 patients. 
Dr. Neiman suggested that five patients be studied that if the treatment is proceeding 
as expected, the entire study can be approved. 
Dr. Parkman asked what the investigators would do if they find tumor growth 
reproducibly occurring in the gene-modified cells of one particular type of tumor. Dr. 
Rosenberg said the TIL cells would be excised from the tumor and grown up. This 
population of cells would be used for therapy. If the investigators do not observe 
responses in a given number of patients, they will move to a different histology. Dr. 
Parkman asked if local tumor growth of modified cells would not represent a safety 
issue. The real issue involves obtaining TIL cells following injection of gene-modified 
tumor cells. Dr. Rosenberg replied that this is how he views the issue. It is 
conceivable that if there were tumor growth and the tumor cells were making cytokine, 
a more effective TIL cell population would be generated at that location. Dr. 
Rosenberg conceded that there is a risk of tumor cells spreading from the local site 
and producing large amounts of the cytokines. 
Dr. Leventhal suggested that the investigators use PCR to see if there are any gene- 
modified cells in the inguinal nodes in the first few patients. 
Dr. Parkman noted that there is no provision in the protocol for removal of the tumor 
if the cells grow at a rapid rate and produce large amounts of cytokine. 
Dr. Leventhal said that the injected cells could grow faster than the resident tumor, 
and the issue will need to be addressed. An arbitrary measurable standard should be 
set, i.e., three weeks for unacceptable growth. Dr. Rosenberg agreed and said that it 
[916] 
Recombinant DNA Research, Volume 14 
