TIL^ S . Some patients who have available tumor may have as part of their 
treatment the addition of cultured lymphocytes taken directly from the tumor. 
If you are such a patient you will be notified. If possible, a section of one 
of your tumors will be surgically removed, and we will try to isolate the 
Ijrmphocytes (a type of immune cell) from within the tumor and grow them in the 
laboratory in large numbers. If this can be accomplished successfully, then 
these lymphocytes -- known as tumor infiltrating lymphocytes (TIL) -- will be 
returned to you by vein immediately before starting the IL-2 and IL-4 
administration. You will receive the lymphocytes intravenously (by vein) . This 
will be followed in two to 24 hours by an infusion by vein of IL-2 
and IL-4 every eight hours for up to five days. To receive the therapy, you will 
be admitted to the hospital for about seven days. After 10 - 14 days you will 
be given a second cycle of treatment when possible. 
The administration of the TIL may cause fever, chills, and shortness of 
breath. Based on our previous experience, these side effects are expected and 
should only last a few hours. Because these lymphocytes are grown from your 
tumor, it is possible that the lymphocytes we return to you may contain tumor 
cells. This may make your condition worse, but we will carefully examine the 
lymphocytes that you are given to decrease the chance that this may occur. 
Gene Marked TIL . 
Although treatment with the tumor infiltrating lymphocytes (TIL) can shrink 
tumors in some patients , many patients do not respond to treatment and even those 
that exhibit shrinkage may show regrowth of the tumor after a short period of 
time (months). Recent scientific advances have made it possible to modify the 
genetic makeup of the the TIL in an effort to make the TIL detectable in your 
body. The scientific advance is called "retroviral -mediated gene transfer" and 
allows us to insert a gene into some of your l 3 nnphocytes . 
If you decide to participate in this part of the study, a gene will be 
inserted into a portion of your lymphocytes by a special laboratory technique. 
These special lymphocytes are referred to as "marked" lymphocytes (or "marked" 
TIL) . A gene is a part of a chromosome (hereditary material) that contains the 
information a cell needs to make proteins. By inserting a gene into your tumor 
infiltrating lymphocytes, we will be able to distinguish these marked lymphocytes 
from all other cells in your body. Thus, we will be able to study some important 
aspects of their life span and function. 
The following procedure will be used to insert gene from bacteria into your 
lymphocytes. Your lymphocytes will be isolated from your tumor as usual. A 
portion of these lymphocytes will have the gene inserted. The gene is attached 
to a harmless virus from mice that can enter your lymphocytes, taking the gene 
with it. 
These "marked" lymphocytes are then grown in the laboratory in large 
numbers. Special tests are performed on these marked lymphocytes to determine 
if they are growing properly with no abnormalities so as to minimize the 
foreseeable risks to you (see below) . If no abnormalities in the marked cells 
are identified, they will be given back to you through your vein along with the 
other unmarked lymphocytes at the appropriate time. 
/P3 
Recombinant DNA Research, Volume 14 
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