II . Brief non-technical description of the proposed experiment. 
TIL (tumor infiltrating lymphocytes) therapy is a new experimental treatment 
for some patients who have advanced cancer. A portion of the tumor is removed, 
grown in the laboratory under conditions which allow the cancer cells to die, 
but the invading immune cells (called lymphocytes) to multiply. These TIL are 
then grown in the laboratory to very large numbers. The TIL which are presumed 
to be the patient's own cancer fighting cells, are infused into a vein of the 
patient. The TIL are thought to circulate through the body, find the areas of 
cancer, and then invade and kill the cancer cells. 
This TIL therapy has resulted in a substantial decrease in tumor size in 
about 40% of patients with melanoma treated thus far. The tumor regressions 
due to this treatment have lasted for varying times from a few months to approximately 
one year. We have also demonstrated that these TIL accumulate in tumor deposits 
after the TIL are injected intravenously. We have been working to improve the 
TIL treatment and have developed evidence to suggest that TIL that are capable of 
secreting a substance with antitumor activity (called tumor necrosis factor or 
TNF) might have increased therapeutic antitumor activity. We have thus developed 
methods for introducing genes into TIL that can increase their production of 
TNF. 
The method that we use for introducing this gene is called retroviral 
mediated gene therapy. In this technique, new genes are inserted into the cells 
using a virus which has been modified so that it can introduce a gene into a 
cell but the virus itself cannot divide and survive. The cells with the new 
gene then produce approximately 10-100 times more TNF than the TILs without the 
introduced gene. 
It is not known whether these gene transduced TIL will have a higher anti- 
tumor activity than normal TIL, although this is a questions that will be, in 
[306] 
Recombinant DNA Research, Volume 14 
